SARS-CoV-2 2697049 COVID-19 Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 202-CoV Shanghai Zerun Biotechnology, Walvax Biotechnology, CEPI VO_0005320 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) AAHI-SC2 ImmunityBio, Inc. VO_0005405 RNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) AAV5-RBD-S Biocad VO_0005336 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Abdala CIGB-66 Center for Genetic Engineering and Biotechnology VO_0005082 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) ABNCoV2 COUGH-1 AdaptVac, Bavarian Nordic, and Radboud University VO_0005255 Virus like particle Clinical trial Intramuscular injection (i.m.) capsid virus-like particle (cVLP) +/- adjuvant MF59 adjuvant MF59 Intramuscular injection (i.m.) ABO1009-DP Suzhou Abogen Biosciences Co., Ltd. VO_0005391 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) ACM-001 ACM Biolabs VO_0005392 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Ad5-nCoV Convidecia, PakVak CanSino Biologics VO_0005144 Recombinant vector vaccine Clinical trial Adenovirus type 5 [Ref5411:Zha, et al., 2020] Intramuscular injection (i.m.) Intramuscular injection (i.m.) SARS-CoV-2 spike protein (Zhu et al., 2020) Anti-RBD antibodies detected at day 14. NAb titers peaked at day 28. TNF-α levels from CD8+ cells were highest in the high dose group. IFN-γ, IL-2 and TNF-α were detected in all groups. (Zhu et al., 2020) Patients were immunized with 5 × 10e10 viral particles per 0·5 mL (low dose), 1 × 10e11 viral particles per mL (middle dose), or 1.5 × 10e11 viral particles per 1·5 mL (high dose). (Zhu et al., 2020) Ad5-triCoV/Mac McMaster University VO_0005339 Recombinant vector vaccine Clinical trial recombinant type 5 replication deficient human adenovirus vector intranasal immunization intranasal immunization S1 region of SARS-CoV-2 spike protein (aa 47-716) and full-length SARS-CoV-2 nucleoprotein (N) fused to a highly conserved portion of the SARS-CoV-2 polymerase (RdRp or POL) AdCLD-CoV19 Cellid Co., Ltd. VO_0004996 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) AdimrSC-2f Adimmune Corp. VO_0005173 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) AG0301-COVID19 AnGes, Inc. VO_0005165 DNA vaccine Clinical trial Intramuscular injection (i.m.) A SARS-CoV-2 DNA vaccine Intramuscular injection (i.m.) spike (S) glycoprotein AG0302-COVID19 AnGes, Inc. VO_0005322 DNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) A cellular immune response was observed in some subjects after AG0302-COVID19 intradermal inoculation (Nakagami et al,, 2022) AG0302-COVID19 is under clinical trial now (NCT04655625) (Nakagami et al,, 2022) Phase II/III: NCT04655625 Age subgroups: 18 years and above Location: Japan AKS-452 University Medical Center Groningen, Akston Biosciences Inc. VO_0004999 Subunit vaccine Clinical trial subcutaneous injection subcutaneous injection Almansour-001 Imam Abdulrahman Bin Faisal University VO_0005393 DNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) ARCoV Academy of Military Science (AMS), Walvax Biotechnology, Suzhou Abogen Biosciences VO_0005161 mRNA vaccine Clinical trial Lipid nanoparticles [Ref5411:Zha, et al., 2020] Intramuscular injection (i.m.) A SARS-CoV-2 mRNA vaccine made of lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 (Zha, et al., 2020) After treament can store Intramuscular injection (i.m.) RBD domain of S protein (Zha, et al., 2020) specific IgG antibodies were readily induced on day 14 after initial immunization, and the booster immunization resulted in a notable increase in IgG titers to ∼1/5,210 and ∼1/22,085 on day 28 after initial immunization. Fifty percent of animals that received high-dose ARCoV immunization developed low-level neutralizing antibodies on day 14 after initial immunization, whereas the booster immunization resulted in a notable increase in NT50 to ∼1/699 and ∼1/6,482 in monkeys vaccinated with low- or high-dose ARCoV, respectively. SARS-CoV-2 RBD-specific T cell responses were stimulated in peripheral blood monocytes (PBMCs) from monkeys vaccinated with a low or high dose of ARCoV on day 5 after booster immunization but not from animals receiving a placebo. There was no significant difference in IL-4+/CD4+ cell response to the SARS-CoV-2 RBD between ARCoV- and placebo-treated animals, suggesting induction of a Th1-biased cellular immune response by ARCoV immunization. (Zhang et al., 2020) Two groups of macaques (n = 10/group) were immunized with 100 or 1,000 μg of ARCoV mRNA-LNP via i.m. administration and boosted with the same dose 14 days after initial immunization. The same number of monkeys (n = 10) was vaccinated with PBS as a placebo. (Zhang et al., 2020) Remarkably, a second immunization with 2 or 10 μg of ARCoV mRNA-LNP resulted in rapid elevation of immunoglobulin G (IgG) and neutralizing antibodies in mice, whereas no SARS-CoV-2-specific IgG and neutralizing antibodies were detected in sera from mice vaccinated with empty LNPs. 28 days after initial immunization, the NT50 titers in mice immunized with 2 or 10 μg of ARCoV mRNA-LNP approached ∼1/2,540 and ∼1/7,079, respectively, and the PRNT50 reached ∼1/2,194 and ∼1/5,704, respectively. (Zhang et al., 2020) There was a significant increase in virus-specific CD4+ and CD8+ effector memory T (Tem) cells in splenocytes from ARCoV-vaccinated mice in comparison with placebo LNPs (Figure 4 A) upon stimulation with peptide pools covering the SARS-CoV-2 RBD. Secretion of interferon γ (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) in splenocytes from mRNA-LNP-immunized mice was significantly higher than in those that received the placebo vaccination. There was no significant difference in IL-4 and IL-6 secretion between ARCoV-immunized animals and placebo-immunized ones, demonstrating that the mRNA-LNP vaccine successfully induces a Th1-biased, SARS-CoV-specific cellular immune response. (Zhang et al., 2020) Female BALB/c mice were immunized i.m. with 2 μg (n = 8) or 10 μg (n = 8) of ARCoV or a placebo (n = 5) and boosted with an equivalent dose 14 days later. Serum was collected 7, 14, 21, and 28 days after initial vaccination. (Zhang et al., 2020) All mice immunized with 2 or 10 μg of ARCoV mRNA-LNP showed full protection against SARS-CoV-2 infection, and no measurable viral RNA was detected in the lungs and trachea , whereas high levels of viral RNA were detected in the lungs and trachea (∼109 and 107 RNA copy equivalents per gram, respectively) of mice in the placebo group. (Zhang et al., 2020) Mice that received two doses of immunization of ARCoV mRNA-LNP at 2 or 10 μg were challenged i.n. with 6,000 plaque-forming units (PFUs) of SARS-CoV-2 MASCp6 40 days after initial vaccination. (Zhang et al., 2020) ARCT-021 LUNAR-COV19 VO_0005164 RNA vaccine Clinical trial Intramuscular injection (i.m.) A SARS-CoV-2 investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the prefusion spike protein of 2019-nCoV formulated in a lipid nanoparticle (Saha et al., 2020) Intramuscular injection (i.m.) spike (S) protein gene (Saha et al., 2020) ARCT-154 Arcturus Therapeutics, Inc. VO_0005347 RNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) ARCT-165 Arcturus Therapeutics, Inc. VO_0005332 RNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) AV-COVID-19 Aivita Biomedical, Inc. VO_0005079 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) AZD2816 AstraZeneca, University of Oxford VO_0005319 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) bacTRL-Spike Symvivo VO_0005174 DNA vaccine Clinical trial Oral Oral Baiya SARS-CoV-2 Vax 1 Baiya Phytopharm Co., Ltd. VO_0005317 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) BBIBP-CorV Beijing Institute of Biological Products, Sinopharm VO_0005166 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) An inactivated whole virus vaccine produced in Vero cells. Intramuscular injection (i.m.) whole virus Before virus challenge at D24, the geometric mean titer of neutralizing antibodies in the low-dose and high-dose groups reached 215 and 256, respectively. (Wang et al., 2020) All macaques were immunized twice on days 0 (D0) and 14 (D14). The placebo group was intramuscularly administered physiological saline, and the two experimental groups were intramuscularly injected with low-dose (2 μg/dose) or high-dose (8 μg/dose) BBIBP-CorV. (Wang et al., 2020) All placebo macaques showed and maintained a high viral load during the whole evaluation period after virus challenge by both throat and anal swabs. In contrast, the viral load in the throat swabs of the low-dose group peaked (5.33 log10copies/mL) at 5 dpi and then decreased to 1.12 log10copies/mL at 7 dpi, which was significantly lower than that of the placebo group. Moreover, no viral load was detected in the anal swabs of two (out of four) macaques in the high-dose group. (Wang et al., 2020) No macaques in the low-dose and high-dose groups had a detectable viral load in any lung lobe, which was significantly different from the results in the placebo group. Furthermore, all macaques that received vaccination showed normal lung with focal mild histopathological changes in few lobes, demonstrating the BBIBP-CorV vaccination could efficiently block the infection of SARS-CoV-2 and COVID-19 disease in monkey. At 7 dpi, the macaques treated with placebo produced low-level NAb with a titer of 1:16, whereas the NAb levels of the vaccinated macaques were highest at 1:2,048 (average 1:860) in the high-dose group and 1:1,024 in the low-dose group (average 1:512). Taken together, all these results demonstrated that both low-dose and high-dose BBIBP-CorV conferred highly efficient protection against SARS-CoV-2 in macaques without observed antibody-dependent enhancement of infection. (Wang et al., 2020) At D24 (10 days after the second immunization), all macaques were intratracheally challenged with l06 TCID50 of SARS-CoV-2 per monkey under anesthesia. (Wang et al., 2020) BBV154 Bharat Biotech VO_0005227 Recombinant vector vaccine Clinical trial Nasal spray Nasal spray This study showed that the vaccine induced in humans high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts (PubMed ID: 32931734) (Hassan et. al 2020). induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. PubMed ID: 32931734 (Hassan et. al 2020) A clinical trial on this vaccine, titled "Safety and Immunogenicity of an Intranasal SARS-CoV-2 Vaccine (BBV154) for COVID-19", is reported: NCT04751682 (https://clinicaltrials.gov/ct2/show/NCT04751682) (NCT04751682). Betuvax-CoV2 Human Stem Cell Institute VO_0005406 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) ChAd-triCoV/Mac McMaster University VO_0005342 Recombinant vector vaccine Clinical trial E1 and E3 deleted replication deficient chimpanzee adenovirus serotype 68 intranasal immunization intranasal immunization S1 region of SARS-CoV-2 spike protein (aa 47-716) and full-length SARS-CoV-2 nucleoprotein (N) fused to a highly conserved portion of the SARS-CoV-2 polymerase (RdRp or POL) ChAdV68-S Gritstone Oncology VO_0005228 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Chinese Academy of Medical Sciences COVID-19 vaccine Covidful VO_0005167 Live, attenuated vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) ChulaCov19 Chulalongkorn University VO_0005175 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) CIGB-669 Center for Genetic Engineering and Biotechnology VO_0005083 Subunit vaccine Clinical trial intranasal immunization intranasal immunization COH04S1 City of Hope Medical Center VO_0005394 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Comirnaty BNT162b2 Pfizer, BioNTech VO_0004987 mRNA vaccine Licensed Lipid nanoparticle Intramuscular injection (i.m.) A SARS-CoV-2 RNA vaccine formed from a lipid nanoparticle-formulated trimerized SARS-CoV-2 receptor-binding domain -70°C ±10°C Intramuscular injection (i.m.) trimerized SARS-CoV-2 receptor-binding domain from S Seven days after Dose 2 (Day 28), the GMCs of S1-binding IgG were 30,339 units (U)/mL (30 μg dose level) and 34,668 U/mL (100 μg dose level). Fifty percent virus neutralisation GMTs, measured by an authentic SARS-CoV-2 neutralisation assay25, were detectable in rhesus macaque sera by Day 21 after Dose 1 and peaked at a GMT of 962 (Day 35, 14 days after Dose 2 of 30 μg) or 1,689 (Day 28, 7 days after Dose 2 of 100 μg; Fig. 3b). Robust GMTs of 285 for 30 μg and 310 for 100 μg dose levels persisted to at least Day 56. Strong IFNγ but minimal IL-4 responses were detected by ELISpot after Dose 2. BNT162b2 elicited strong S-specific IFNγ producing T-cell responses, including a high frequency of CD4+ T cells that produced IFNγ, IL-2, and TNF but a low frequency of CD4+ T cells that produced IL-4, indicating a TH1-biased response. BNT162b2 also elicited S-specific IFNγ+ producing CD8+ T cells. (Vogel et al., 2020) Groups of six male, 2-4 year old rhesus macaques were immunized IM with 30 or 100 μg of BNT162b2 or saline control on Days 0 and 21. (Vogel et al., 2020) BNT162b2 immunization prevented lung infection in 100% of the SARS-CoV-2 challenged rhesus macaques, with no viral RNA detected in the lower respiratory tract of immunized and challenged animals. The BNT162b2 vaccination also cleared the nose of detectable viral RNA in 100% of the SARS-CoV-2 challenged rhesus macaques within 3 days after the infection. (Vogel et al., 2020) Six rhesus macaques that had received two immunisations with 100 μg BNT162b2 and three age-matched macaques that had received saline were challenged 55 days after Dose 2 with 1.05 × 106 plaque forming units of SARS-CoV-2 (strain USA-WA1/2020), split equally between intranasal and intratracheal routes. Three additional non-immunised, age-matched rhesus macaques (sentinels) were mock-challenged with cell culture medium. (Vogel et al., 2020) BNT162b2 elicited strong antibody responses, with S-binding IgG concentrations above those in a COVID-19 human convalescent sample (HCS) panel. Day 29 (7 days post-boost) SARS-CoV-2 serum 50% neutralising geometric mean titers were 0.3-fold (1 µg) to 3.3-fold (30 µg) those of the HCS panel. The BNT162b2-elicited sera neutralized pseudoviruses with diverse SARS-CoV-2 S variants. In most participants, S-specific CD8+ and T helper type 1 (TH1) CD4+ T cells had expanded, with a high fraction producing interferon-γ (IFNγ). CD8+ T cells were shown to be of the early-differentiated effector-memory phenotype, with single specificities reaching 0.01-3% of circulating CD8+ T cells. Vaccination with BNT162b2 at well tolerated doses elicits a combined adaptive humoral and cellular immune response, which together may contribute to protection against COVID-19. (Sahin et al., 2020) Participants 19-55 years of age were vaccinated with BNT162b2 in Germany. Twelve participants per dose cohort were assigned to receive a priming dose of 1, 10, 20 or 30 μg on day 1 and a booster dose on day 22. (Sahin et al., 2020) No serious adverse events (SAE) and no withdrawals due to related adverse events (AEs) were observed at any dose level. Local reactions, predominantly pain at the injection site, were mild to moderate (grade 1 and 2) and were similar in frequency and severity after the priming and booster doses. The most common systemic AEs were fatigue followed by headache and only two participants reported fever, which was mild. Transient chills were more common after the boost, dose-dependent, and occasionally severe. Muscle pain and joint pain were also more common after the boost and showed dose-dependent severity. There were no grade 4 reactions. Generally, reactions had their onset within 24 hours of immunisation, peaked on the day after immunisation, and mostly resolved within 2-3 days. Reactions did not require treatment or could be managed with simple measures (e.g. paracetamol). (Sahin et al., 2020) Corbevax Biological E VO_0005081 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) CoronaVac PiCoVacc Sinovac Biotech Ltd VO_0005141 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) A purified inactivated SARS-CoV-2 virus vaccine(Gao et al., 2020) The virus was propagated in a 50-liter culture of Vero cells using the Cell Factory system and inactivated by using β-propiolactone The virus was purified using depth filtration and two optimized steps of chromatography, yielding a highly pure preparation of PiCoVacc. (Gao et al., 2020) Intramuscular injection (i.m.) Whole virus (Gao et al., 2020) SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated mice and peaked at the titer of 819,200 (>200 μg/ml) and 409,600 (>100 μg/ml), respectively, at week 6(Gao et al., 2020) BALB/c mouse Mice were vaccinated at day 0 and 7 with either 1.5 μg/dose, 3.0 μg/dose, or 6.0 μg/dose on both days. (Gao et al., 2020) BALB/c mice were injected with vaccine 5761 at days 0 and 7.(Gao et al., 2020) Immune Response Description: SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated rats and the maximum neutralizing titers reached 2,048-4,096 at week 7 (Gao et al., 2020) Wistar Rats were vaccinated at day 0 and 7 with either 1.5 μg/dose, 3.0 μg/dose, or 6.0 μg/dose on both days.(Gao et al., 2020) . S-specific IgG and NAb were induced at week 2 and rose to ~12,800 and ~50, respectively at week 3 after vaccination in both vaccinated groups, whose titers are similar to those of serum from the recovered COVID-19 patients. NAb titer (61) in the medium dose immunized group were ~20% greater than that observed (50) in the high dose vaccinated group at week 3, removing the outlier instead have medium dose group be ~40% lower than that in the high dose group (Gao et al., 2020) Rhesus macaque Macaques were immunized three times via the intramuscular route with medium (3 μg per dose) or high doses (6 μg per dose) of PiCoVacc at day 0, 7 and 14 (n=4)(Gao et al., 2020) argely protected against SARS-CoV-2 infection with very mild and focal histopathological changes in a few lobes of lung, which probably were caused by a direct inoculation of 106 TCID50 of virus into the lung through intratracheal route, that needed longer time (more than one week) to recover completely (Gao et al., 2020). No serious pathology recorded at day 29 in vaccinated groups (Gao et al., 2020) Challenge protocol involved direct inoculation of 1e6 TCID50 of SARS-CoV-2 CN1 into the animal lung through the intratracheal route at day 22 (one week after the third immunization and after immune response results were recorded) (Gao et al., 2020). CORVax12 Providence Health & Services, OncoSec Medical Inc. VO_0005183 DNA vaccine Clinical trial Intradermal injection (i.d.) Intradermal injection (i.d.) CoV2 SAM GlaxoSmithKline VO_0005156 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) CoV2-OGEN1 US Specialty Formulations, VaxForm VO_0005263 Subunit vaccine Clinical trial Oral Oral COVAC Vaccine and Infectious Disease Organization, Seppic, Vaccine Formulation Institute (VFI) VO_0005194 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVAX-19 SpikoGen Vaxine, CinnaGen VO_0005193 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVAXIN BBV152 Bharat Biotech VO_0004991 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Alhydroxiquim-II (Ella et al., 2021) COVAXIN is made up of an inactivated SARS-CoV-2 virus that activates the immune system to create antibodies againt the virus. When preparing the vaccine, Beta-propiolactone, an organic compound, inactivates the virus by binding to its genes. The vaccine itself contains the RNA of the virus surrounded by a protein shell that cannot be replicated. It also contains an adjuvant, Alhydroxiquim-II, which includes a molecule attached to Alhydrogel (alum used in many adjuvants). After injection of the vaccine, the adjuvant moves to the lymph nodes, where it separates from the alum and attaches to two cell receptors, activating a TLR7/8 agonist and Th1 immune system response. The virus contains a receptor on its outer-shell which is adsobrded to the adjuvant. (Ella et al., 2021) (LABline, 2021)(Thiagarajan, 2021) Intramuscular injection (i.m.) We evaluated anti-SARS-CoV-2 Immunoglobulin-G (IgG) antibody and neutralizing antibody (NAb) titers from the serum samples during the immunization phase (0, 12, 19, 26 and 28 days) and after SARS-CoV-2 infection (0, 1, 3, and 7). IgG levels were detectable from 3rd-week post-immunization and were found increasing till 35th day [7 days post-infection (DPI)]. Group III showed the highest IgG titer (1:25600) compared to group II and IV (1:1600-1:6400). The highest NAb titers of 1:209 to 1:5,217 were detected in group III after the SARS-CoV-2 challenge. The NAb titers for groups II and IV were (1:87.4 - 1: 3974) and (1:29.5 -1: 3403) respectively. These NAb titers correlated with the IgG antibody titers. NAb and IgG response was not detectable in the placebo group. Twenty adult rhesus macaques aged 3 - 12 years were divided into 4 groups of five animals (3 M, 2 F) each viz. the placebo (group I), group II, III, and IV. The placebo group was administered Phosphate buffer saline (PBS), group II, III, and IV were immunized with formulations of purified inactivated SARS-CoV-2 vaccine candidate 6μg+Adjuvant-A(BBV152C), 3μg+Adjuvant-B (BBV152A), and 6μg+Adjuvant-B (BBV152B) respectively. Animals were administered with two doses of vaccine/placebo on days 0 and 14 respectively intramuscularly in the deltoid region. Blood samples were collected on 0, 12, 19, 26, and 28 days for assessing the anti-SARS IgG antibody and NAb titers. Vaccinated groups had a detectable level of gRNA from 1 to 5 DPI with viral clearance on 7 DPI (Figure 2B). sgRNA was not detected in TS specimens of animals from either group. In the vaccinated groups, gRNA was detected in BAL specimens until 3 DPI (Figure 2C). sgRNA was detected in BAL specimens of four out of five animals of the placebo group, while it was not detected in BAL specimens of vaccinated groups. Except for the placebo group, none of the vaccinated groups showed the presence of gRNA in lung lobes (Figure 2D). The comparisons of viral copy numbers of the NS, TS, and the BAL fluid samples of the vaccinated as compared to the placebo group were found to be statistically significant using the two-tailed Mann-Whitney test. Adverse events were not seen in animals immunized with a two-dose vaccination regimen. After completion of twenty eight-days of immunization, animals were challenged with 1 ml of SARS-CoV-2 (P-3, NIV-2020770, TCID50 106.5/ml)19 intratracheally and 0.25 ml in each nostril. NS, TS, rectal swab, chest X-ray, blood specimens, and BAL fluid were collected on 0, 1, 3, 5, and 7 DPI. IgG titres (GMTs) to all epitopes (spike protein, receptor-binding domain, and nucleocapsid protein) increased rapidly after the administration of both doses. Both 3 μg and 6 μg with Algel-IMDG groups reported similar anti-spike, anti-receptor binding, and anti-nucleoprotein IgG titres (GMTs), adding to the dose-sparing effect of the adjuvant. The mean isotyping ratios (IgG1/IgG4) were greater than 1 for all vaccinated groups, which was indicative of a Th1 bias. Seroconversion rates (after the second dose), based on MNT50 were 87·9% (95% CI 79·8–94·3) in the 3 μg with Algel-IMDG group, 91·9% (84·6–96·0) in the 6 μg with Algel-IMDG group, and 82·8% (73·7–89·2) in the 6 μg with Algel group. Seroconversion (at day 28) in the control group was reported in six (8% [3·6–17·2]) of 75 participants, suggestive of asymptomatic infection. The vaccine-induced responses were similar to those observed in the convalescent serum collected from 41 patients who had recovered from COVID-19 (figure 3B). On these 41 patients, the median titre of symptomatic patients (n=25; median 142·2 [IQR 56·6–350]) was significantly higher than that of the asymptomatic patients (n=16; 22·6 [9·0–56·5]).Randomly selected serum samples from day 28 were analysed by PRNT50 at the National Institute of Virology with homologous and heterologous strain assessments. Neutralisation responses, regardless of the challenge strain, were observed. In a subset of randomly selected blood samples at one site, IFN-γ ELISpot responses against SARS-CoV-2 peptides peaked at about 100–120 spot-forming cells per million peripheral blood mononuclear cells in all vaccinated groups on day 28. Both the Algel-IMDG groups elicited CD3+, CD4+, and CD8+ T-cell responses that were reflected in the IFN-γ production, albeit in a small number of samples. However, there was a minimal detection of less than 0·5% of CD3+, CD4+, and CD8+ T-cell responses in the 6 μg with Algel group and the Algel only group. [Ella et al., 2021] A double-blind, multicentre, randomised, controlled phase 1 trial was conducted to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18–55 years who were deemed healthy by the investigator were eligible. The vaccine candidates were formulated with two adjuvants: Algel (alum) and Algel-IMDG, an imidazoquinoline class molecule (TLR7 and TLR8 agonist) adsorbed onto Algel. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. The vaccine (BBV152) and the control were provided as a sterile liquid that was injected intramuscularly (deltoid muscle) at a volume of 0·5 mL/dose in a two-dose regimen on day 0 (day of randomisation) and day 14. [Ella et al., 2021] Because this is an interim report, we are not reporting any data on the persistence of vaccine-induced antibody responses or long-term safety outcomes. The results reported here do not permit efficacy assessments. The analysis of safety outcomes requires more extensive phase 2 and 3 clinical trials. [Ella et al., 2021] CoVepiT OSE Immunotherapeutics VO_0005261 Subunit vaccine Clinical trial subcutaneous injection subcutaneous injection Covi Vax NRC-VACC-101 National Research Centre, Egypt VO_0005349 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) A human coronavirus (hCoV)-19/Egypt/NRC-03/2020 SARS-CoV-2 strain COVI-VAC Codagenix, Inc. VO_0005187 Live, attenuated vaccine Clinical trial intranasal immunization intranasal immunization COVID-19 aAPC vaccine Shenzhen Geno-Immune Medical Institute VO_0005184 Recombinant vector vaccine Clinical trial subcutaneous injection subcutaneous injection COVID-19 DNA vaccine by the University of Hong Kong and Immuno Cure 3 Limited University of Hong Kong and Immuno Cure 3 Limited VO_0005346 DNA vaccine Licensed Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVID-19 inactivated vaccine by the Scientific and Technological Research Council of Turkey Scientific and Technological Research Council of Turkey (TÜBITAK) VO_0005257 Inactivated or "killed" vaccine Clinical trial subcutaneous injection Adjuvanted inactivated vaccine against SARS-CoV-2 Aluminium hydroxide and CpG oligodeoxynucleotides subcutaneous injection COVID-19 mRNA vaccine by CanSino Biologics CanSino Biologics Inc. VO_0005407 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVID-19 mRNA vaccine by Shanghai East Hospital and Stemirna Therapeutics Shanghai East Hospital and Stemirna Therapeutics VO_0005260 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVID-19 rNDV vector vaccine by Laboratorio Avi-Mex Laboratorio Avi-Mex VO_0005259 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVID-19 subunit vaccine by HIPRA Laboratorios Hipra, S.A. VO_0005321 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVID-19 subunit vaccine by National Vaccine and Serum Institute of China National Vaccine and Serum Institute of China VO_0005248 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVID-19 subunit vaccine by PT Bio Farma PT Bio Farma VO_0005343 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVID-eVax Takis, Rottapharm Biotech VO_0005230 DNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVIDITY Scancell Ltd. VO_0005344 DNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Needle free injection A clinical trial on this vaccine is conducted, with the clinical trial ID - NCT05047445: (NCT05047445 - COVIDITY) Covifenz CoVLP Medicago Inc. VO_0004992 Virus Like Particle Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVIGEN University of Sydney, Bionet Co., Ltd, Technovalia VO_0005231 DNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Covigenix VAX-001 Entos Pharmaceuticals VO_0005186 DNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVIran Barakat Shifa Pharmed Industrial Co VO_0005229 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) CoviVac (Russia) Chumakov Centre at the Russian Academy of Sciences VO_0005243 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) COVIVAC (Vietnam) Institute of Vaccines and Medical Biologicals, Vietnam VO_0005246 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) CV2CoV VO_0005168 RNA vaccine Clinical trial Intramuscular injection (i.m.) A SARS-CoV-2 mRNA vaccine developed by CureVac AG and CEPI (NCT04449276) Intramuscular injection (i.m.) CVXGA1 CyanVac LLC VO_0005318 Recombinant vector vaccine Clinical trial intranasal immunization intranasal immunization DelNS1-2019-nCoV-RBD-OPT1 University of Hong Kong, Xiamen University, Beijing Wantai Biological Pharmacy VO_0005087 Recombinant vector vaccine Clinical trial intranasal immunization intranasal immunization DoCo-Pro-RBD-1 + MF59 University of Melbourne VO_0005395 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) DS-5670a Daiichi Sankyo Co., Ltd. VO_0005245 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) EG-COVID EyeGene Inc. VO_0005408 RNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) EgyVax Eva Pharma VO_0005396 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) EpiVacCorona FBRI State Research Center of Virology and Biotechnology VO_0005088 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) EuCorVac-19 EuBiologics Co., Ltd. VO_0005232 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) EXG-5003 Elixirgen Therapeutics, Inc. VO_0005249 mRNA vaccine Clinical trial Intradermal injection (i.d.) Intradermal injection (i.d.) GEMCOVAC-19 Gennova Biopharmaceuticals Limited VO_0005413 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) GLS-5310 GeneOne Life Science, Inc. VO_0005089 DNA vaccine Clinical trial Intradermal injection (i.d.) Intradermal injection (i.d.) GRAd-CoV2 ReiThera VO_0005169 Recombinant vector vaccine Clinical trial Gorilla adenovirus [Ref5459:NCT04528641] Intramuscular injection (i.m.) A SARS-CoV 2 recombinant viral vector using Gorilla Adenovirus that encodes for SARS-CoV-2 Spike protein. (NCT04528641) Intramuscular injection (i.m.) SARS-CoV-2 S protein (NCT04528641) GRT-R912 Gritstone Bio, Inc. VO_0005397 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) GX-19 Genexine VO_0005170 DNA vaccine Clinical trial Intramuscular injection (i.m.) A SARS-CoV-2 DNA vaccine expressing the SARS-CoV-2 S protein (NCT04445389) Intramuscular injection (i.m.) S protein (NCT04445389) hAd5-COVID-19 ImmunityBio, Inc.; NantKwest Inc. VO_0005189 Recombinant vector vaccine Clinical trial subcutaneous injection subcutaneous injection HDT-301 repRNA-CoV2S SENAI CIMATEC VO_0005256 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with lipid inorganic nanoparticles (LIONs) that were designed to enhance vaccine stability, delivery, and immunogenicity. (Erasmus et al., 2020) Intramuscular injection (i.m.) full-length spike (S) protein IIBR-100 Israel Institute for Biological Research, Weizmann Institute of Science VO_0005090 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) IMP CoVac-1 University Hospital Tuebingen VO_0005190 Subunit vaccine Clinical trial subcutaneous injection subcutaneous injection IN-B009 HK inno.N Corporation VO_0005351 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) INO-4800 Inovio Pharmaceuticals VO_0005172 DNA vaccine Clinical trial pGX9501 plasmid [Ref5462:Smith et al., 2020] Intradermal injection (i.d.) A DNA vaccine that expresses S protein from the pGX9501 vector(Smith et al., 2020) Intradermal injection (i.d.) S protein (Smith et al., 2020) By week 6, 95% (36/38) of the participants seroconverted based on their responses by generating binding (ELISA) and/or neutralizing antibodies (PRNT IC50), with responder geometric mean binding antibody titers of 655.5 [95% CI (255.6, 1681.0)] and 994.2 [95% CI (395.3, 2500.3)] in the 1.0 mg and 2.0 mg groups, respectively. For neutralizing antibody, 78% (14/18) and 84% (16/19) generated a response with corresponding geometric mean titers of 102.3 [95% CI (37.4, 280.3)] and 63.5 [95% CI (39.6, 101.8)], in the respective groups. By week 8, 74% (14/19) and 100% (19/19) of subjects generated T cell responses by IFN-ɣ ELISpot assay with the median SFU per 106 PBMC of 46 [95% CI (21.1, 142.2)] and 71 [95% CI (32.2, 194.4)] in the 1.0 mg and 2.0 mg groups, respectively. Flow cytometry demonstrated a T cell response, dominated by CD8+ T cells co-producing IFN-ɣ and TNF-α, without increase in IL-4. (Tebas et al., 2020) INO-4800 was evaluated in two groups of 20 participants, receiving either 1.0 mg or 2.0 mg of vaccine intradermally followed by CELLECTRA® EP at 0 and 4 weeks. Thirty-nine subjects completed both doses; one subject in the 2.0 mg group discontinued trial participation prior to receiving the second dose. ClinicalTrials.gov identifier: NCT04336410. (Tebas et al., 2020) Through week 8, only 6 related Grade 1 adverse events in 5 subjects were observed. None of these increased in frequency with the second administration. No serious adverse events were reported. (Tebas et al., 2020) Neutralization ID50 average titers of 92.2 were observed in INO-4800 immunized mice. No reduction in RLU (relative luciferase units) was observed for the control animals. Sera from INO-4800 immunized BALB/c mice neutralized both SARS-CoV-2/WH-09/human/2020 and SARS-CoV-2/Australia/VIC01/2020 virus strains with average ND50 titers of 97.5 and 128.1, respectively. Sera from INO-4800 immunized C57BL/6 mice neutralized wildtype SARS-CoV-2 virus with average ND50 titer of 340. Inhibition of the Spike-ACE2 interaction was compared using serum IgG from a naïve mouse and from an INO-4800 vaccinated mouse. The receptor inhibition assay was repeated with a group of five immunized mice, and demonstrating that INO-4800-induced antibodies competed with ACE2 binding to the SARS-CoV-2 Spike protein. (Smith et al., 2020) Flow cytometric analysis on splenocytes harvested from BALB/c mice on Day 14 after a single INO-4800 immunization revealed the T cell compartment to contain 0.04% CD4+ and 0.32% CD8+ IFN-γ+ T cells after stimulation with SARS-CoV-2 antigens. (Smith et al., 2020) CoV vaccine-induced immunopathology utilized the BALB/c mouse, a model known to preferentially develop Th2-type responses. The DNA vaccine platform induces Th1-type immune responses and has demonstrated efficacy without immunopathology in models of respiratory infection. (Smith et al., 2020) BALB/c mice were immunized twice with 10 micrograms of INO-4800, on days 0 and 14, and sera was collected on day 7 post-second immunization. (Smith et al., 2020) Johnson & Johnson COVID-19 vaccine Ad26.COV2.S JNJ-78436735 Janssen Pharmaceutica VO_0005159 Recombinant vector vaccine Clinical trial adenovirus serotype 26 (Ad26) [Ref5451:Mercado et al., 2020] intranasal immunization A recombinant viral vector virus using adenovirus serotype26 vector experssing the S protein (Mercado et al., 2020). Ad26.COV2.S is currently undergoing a Phase III clinical trial: (NCT04505722) intranasal immunization S protein with tissue plasminogen activator leader sequence and two proline stabilizing mutations (Mercado et al., 2020) Recombinant vector construction The S protein gene is engineered to be added to the Ad viral vaccine vector for expression (Mercado et al., 2020). Liver titer neutralizing antibodies present (median 113; range 53-233) (Mercado et al., 2020). Presence of INF-gamma response but minimal to no IL-4 response (Mercado et al., 2020). NAb titers as measured by both assays were observed in the majority of vaccinated animals at week 2 and generally increased by week 4. The Ad26-S.PP vaccine elicited the highest pseudovirus NAb titers (median 408; range 208–643) and live virus NAb titers (median 113; range 53–233) at week 4. The Ad26-S.PP vaccine also induced detectable S-specific IgG and IgA responses in bronchoalveolar lavage (BAL). Cellular immune responses were induced in 30 of 32 vaccinated animals at week 4. A single immunization of 1011 vp Ad26-S.PP elicited consistent IFN-γ ELISPOT responses but minimal to no IL-4 ELISPOT responses, suggesting induction of Th1-biased responses. (Mercado et al., 2020) Immunized vector with Ad26 vaccine with immunization of 10^11 viral particles by the intramuscular route on week 0. Complete protection called due to no detecable vius in bronchoalveolar lavage with limit of detectin of 1.69log10sgRNAcopies/Ml (Mercado et al., 2020). Macaques that were treated with Ad26-S.PP had no detectable virus in BAL samples. Only one of the macaques that received the Ad26-S.PP vaccine showed a low amount of virus in nasal swabs. All vaccinated macaques showed no detectable infectious virus in nasal swabs by plaque-forming unit (PFU) assays. A comparison of peak viral loads in the vaccinated macaques suggested that protection in BAL samples was generally more robust than in nasal swabs (Fig. 5). The Ad26-S.PP vaccine provided complete protection in both the lower and upper respiratory tract with the exception of one macaque that showed a low amount of virus in nasal swabs, and resulted in greater than 3.2 and 3.9 log10-transformed reductions of median peak sgRNA in BAL and nasal swabs, respectively, as compared with sham controls (P < 0.0001 and P < 0.0001, respectively, two-sided Mann–Whitney tests) (Fig. 5). Among the 32 vaccinated macaques, 17 were completely protected and had no detectable sgRNA in BAL or nasal swabs after challenge, and 5 additional macaques had no sgRNA in BAL but showed some virus in nasal swabs. (Mercado et al., 2020) Week 6 after initial vaccination had each animal exposed to 1^4 TCID50 SARS-CoV2 vy the intranasal and intratracheal routes (Mercado et al., 2020). KBP-COVID-19 VO_0005171 Subunit vaccine Clinical trial Intramuscular injection (i.m.) A SARS-CoV-2 subunit vaccine with a protein subunit.(Saha et al., 2020) Intramuscular injection (i.m.) RBD domain of S protein (Saha et al., 2020) KCONVAC Shenzhen Kangtai Biological Products Co., Ltd.; Beijing Minhai Biotechnology Co. VO_0005084 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) KD-414 KM Biologics Co., Ltd. VO_0005250 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine Kocak Farma VO_0005253 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) whole virus licensed COVID-19 human vaccine Generic Unknown VO_0004908 Other: mRNA vaccine Licensed A generic representation of mRNA vaccines used to prevent COVID-19 infection in humans. These vaccines deliver messenger RNA encoding the SARS-CoV-2 spike protein, prompting an immune response without using live virus. LNP-nCOV saRNA-02 MRC/UVRI and LSHTM Uganda Research Unit VO_0005276 RNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) LNP-nCoVsaRNA COVAC1 Imperial College London VO_0005143 RNA Vaccine Clinical trial Lipid nanoparticle (LNP)[Ref5418:McKay et al., 2020] Intramuscular injection (i.m.) A SARS-CoV-2 vaccine made of self-coding RNA encoding SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (McKay et al., 2020). Intramuscular injection (i.m.) spike (S) protein (McKay et al., 2020) LV-SMENP-DC Shenzhen Geno-Immune Medical Institute VO_0005091 Recombinant vector vaccine Clinical trial subcutaneous injection subcutaneous injection LVRNA009 AIM Vaccine Co., Ltd. VO_0005414 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Phase I: NCT05364047 Phase II: NCT05352867 Intramuscular injection (i.m.) serum samples from mice immunized with monovalent Delta vaccine showed relatively low virus neutralization titers (VNTs) against the pseudotyped virus of the Omicron strains. Serum samples from mice immunized with bivalent Delta/BA.1 vaccine had high VNTs against the pseudotyped Wuhan-Hu-1, Delta, and BA.1 strains but low VNTs against BA.2 and BA.5 (p &lt; 0.05). Serum samples from mice immunized with Delta/BA.2 vaccine had high VNTs against the pseudotyped Wuhan-Hu-1, Delta, BA.1 and BA.2 strains but low VNTs against BA.5. Finally, serum samples from mice immunized with Delta/BA.5 vaccine had high VNTs against all the tested pseudotyped SARS-CoV-2 strains including the Wuhan-Hu-1, Delta, and Omicron variants (p &gt; 0.05).(Li et al., 2022) LYB001 Yantai Patronus Biotech Co., Ltd. VO_0005348 Virus Like Particle Clinical trial Intramuscular injection (i.m.) Phase I: NCT05125926 (NCT05125926) Intramuscular injection (i.m.) The study vaccine will be administered IM at upper arm deltoid as a three-dose regimen with 28d interval on day 0, 28, 56. This is a randomized, double-blind, placebo-controlled Phase Ⅰ trial in healthy adults aged 18 years and older, intended to evaluate the safety, reactogenicity, and immunogenicity profile of LYB001 (NCT05125926) MF59-adjuvanted SARS-CoV-2 Sclamp vaccine The University of Queensland VO_0005258 Subunit vaccine Clinical trial Intramuscular injection (i.m.) squalene adjuvant MF59C (Chappell et al., 2021) Intramuscular injection (i.m.) The SARS-CoV-2 sclamp antigen comprises a trimeric glycosylated SARS-CoV-2 spike glycoprotein ectodomain fused to a molecular clamp. (Chappell et al., 2021) MIPSCo-mRNA-RBD-1 University of Melbourne VO_0005398 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Moderna COVID-19 vaccine mRNA-1273 Moderna VO_0005157 mRNA vaccine Licensed lipid nanoparticle [Ref5456:Wang et al., 2020] Intramuscular injection (i.m.) A SARS-CoV2 RNA vaccine made of lipid nanoparticle with mRNA which encodes the S-2P antigen, made of the SARS-CoV-2 glycoprotein with a transmembrane anchor and intact S1-S2 cleavage site (Wang et al., 2020). Intramuscular injection (i.m.) S-2P antigen, made of the SARS-CoV-2 glycoprotein with a transmembrane anchor and intact S1-S2 cleavage site (Wang et al., 2020). The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. (Corbett et al., 2020) Animals were vaccinated intramuscularly at week 0 and at week 4 with either 10 or 100 μg of mRNA-1273 in 1 ml of 1× phosphate-buffered saline (PBS) into the right hind leg. (Corbett et al., 2020) Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. (Corbett et al., 2020) At week 8 (4 weeks after the second vaccination), all animals were challenged with a total dose of 7.6×105 plaque-forming units (PFU). The stock of 1.9×105 PFU per milliliter SARS-CoV-2 (USA-WA1/2020 strain) was administered in a volume of 3 ml by the intratracheal route and in a volume of 1 ml by the intranasal route (0.5 ml per nostril). (Corbett et al., 2020) By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. (Anderson et al., 2020) All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. (Anderson et al., 2020) The mRNA-1273 vaccine was administered as a 0.5-ml intramuscular injection into the deltoid on days 1 and 29 of the study. Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. (Anderson et al., 2020) mRNA-1073 Moderna VO_0005409 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) mRNA-1273.211 Moderna VO_0005277 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group. (Ali et al., 2021) The mRNA-1273 vaccine had an acceptable safety profile in adolescents. (Ali et al., 2021) the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively) (Ali et al., 2021) mRNA-1273.214 Moderna VO_0005415 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) In this ongoing, phase 2-3 study, we compared the 50-μg bivalent vaccine mRNA-1273.214 (25 μg each of ancestral Wuhan-Hu-1 and omicron B.1.1.529 [BA.1] spike messenger RNAs) with the previously authorized 50-μg mRNA-1273 booster (Chalkias et al., 2022) Vaccine effectiveness was not assessed in this study; in an exploratory analysis, SARS-CoV-2 infection occurred in 11 participants after the mRNA-1273.214 booster and in 9 participants after the mRNA-1273 booster. The bivalent omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without evident safety concerns. (Chalkias et al., 2022) mRNA-1273.351 Moderna, NIAID VO_0005233 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) mRNA-1273.529 Moderna VO_0005416 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. (Ying et al., 2022) mRNA-1283 Moderna VO_0005185 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) MRT5500 Sanofi Pasteur, Translate Bio VO_0005241 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) MV-014-212 Meissa Vaccines, Inc. VO_0005240 Live, attenuated vaccine Clinical trial intranasal immunization MV-014-212, is a live attenuated vaccine against respiratory syncytial virus (RSV) that is expressing the spike (S) protein of SARS-CoV-2. MV-014-212 is administered as drops or a spray in the nose. intranasal immunization Spike Protein of SARS-CoV-2 MVA-SARS-2-S Universitätsklinikum Hamburg-Eppendorf, Ludwig-Maximilians - University of Munich VO_0005191 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) MVA-SARS-2-ST Hannover Medical School VO_0005262 Recombinant vector vaccine Clinical trial Inhaled Inhaled MVC-COV1901 Medigen, Dynavax VO_0005192 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) naNO-COVID Emergex Vaccines Holding Ltd. VO_0005350 Subunit vaccine Clinical trial Intradermal injection (i.d.) Intradermal injection (i.d.) Nanocovax Nanogen Pharmaceutical Biotechnology VO_0005092 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) A viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. (Tran et. al 2021) Nanocovax did not induce any adverse effects in mice (Mus musculus var. albino) and rats (Rattus norvegicus). (Tran et. al 2021) NBP2001 SK Bioscience Co., Ltd. VO_0005234 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) NDV-HXP-S Icahn School of Medicine at Mount Sinai, Mahidol University VO_0005235 Recombinant vector vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Noora Bagheiat-allah University of Medical Sciences VO_0005316 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) NVX-CoV2373 Covovax Novavax VO_0005155 Subunit vaccine Clinical trial Intramuscular injection (i.m.) A recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. (Keech et al., 2020) Matrix-M1 (Keech et al., 2020) Intramuscular injection (i.m.) SARS-CoV-2 spike (S) glycoprotein (Keech et al., 2020) Animals immunized with a single priming dose of 0.1–10 μg NVX-CoV2373/Matrix-M had elevated anti-S IgG titers that were detected 21–28 days after a single immunization. Mice immunized with 10 μg NVX-CoV2373/Matrix-M induced antibodies that blocked hACE2 receptor binding to S-protein and virus neutralizing antibodies 21–28 days after a single priming dose. Animals immunized with the prime/boost regimen had significantly elevated anti-S IgG titers that were detected 7–16 days following the booster immunization across all dose levels. Animals immunized with 1 μg and 10 μg NVX-CoV2373/Matrix-M had similar high anti-S IgG titers following immunization (geometric mean titer, GMT = 139,000 and 84,000, respectively). Importantly, mice immunized with 0.1 μg, 1 μg, or 10 μg NVX-CoV/Matrix-M had significantly (p ≤ 0.00006) higher anti-S IgG titers compared to mice immunized with 10 μg NVX-CoV2373 without adjuvant. Immunization with two doses of NVX-CoV2373/Matrix-M elicited high titer antibodies that blocked hACE2 receptor binding to S-protein (IC50 = 218–1642) and neutralized the cytopathic effect (CPE) of SARS-CoV-2 on Vero E6 cells (100% blocking of CPE = 7680–20,000) across all dose levels. (Tian et al., 2021) Groups of mice were immunized with a dose range (0.01 μg, 0.1 μg, 1 μg, and 10 μg) of NVX-CoV2373 with 5 μg Matrix-M adjuvant using a single priming dose or a prime/boost regimen spaced 14 days apart. (Tian et al., 2021) At 4 days post infection (dpi), placebo-treated mice had an average of 104 SARS-CoV-2 pfu/lung, while the mice immunized with NVX-CoV2373 without Matrix-M had 103 pfu/lung and those with Matrix-M had limited to no detectable virus load. The NVX-CoV2373 with Matrix-M prime-only groups of mice exhibited a dose-dependent reduction in virus titer, with recipients of the 10 μg dose having no detectable virus at day 4 post infection. Mice receiving 1 μg, 0.1 μg, and 0.01 μg doses all showed a marked reduction in titer compared to placebo-vaccinated mice. In the prime/boost groups, mice immunized with 10 μg, 1 μg, and 0.1 μg doses had almost undetectable lung virus loads. These results confirmed that NVX-CoV2373 confers protection against SARS-CoV-2 and that low doses of the vaccine associated with lower serologic responses do not exacerbate weight loss or induce exaggerated illness. (Tian et al., 2021) Mice were immunized with a single priming dose or a prime/boost regimen with NVX-CoV2373/Matrix-M as described above. Since mice do not support replication of WT SARS-CoV-2 virus, BALB/c mice were transduced with adenovirus encoding human ACE2 receptor (Ad/hACE2) which renders them permissive to infection with SARS-CoV-2 (refs. 21,22). At 4 days post transduction, mice were challenged with 105 plaque forming units (pfu)/mouse of SARS-CoV-2 (WA1 strain). Following challenge, mice were weighed daily and pulmonary histology and viral load were analyzed at 4 and 7 days post challenge. (Tian et al., 2021) Omicron COVID-19 inactivated vaccine by China National Biotec Group Company Limited China National Biotec Group Company Limited VO_0005417 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Osvid-19 Osve Pharmaceutical Company VO_0005399 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Oxford-AstraZeneca COVID-19 vaccine ChAdOx1 nCoV19 vaccine AZD1222 AstraZeneca VO_0005158 Recombinant vector vaccine Clinical trial chimpanzee adenovirus-vectored vaccine (ChAdOx1) [Ref5425:Folegatti et al., 2020] Intramuscular injection (i.m.) A chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein (Folegatti et al., 2020) Intramuscular injection (i.m.) SARS-CoV-2 spike protein (Folegatti et al., 2020) Spike-specific antibodies were present as early as 14 days after vaccination and were significantly increased after the second immunization. Endpoint IgG titres of 400–6,400 (prime) and 400–19,200 (prime–boost) were measured on the day of challenge. Virus-specific neutralizing antibodies were also significantly increased after secondary immunization and detectable in all vaccinated animals before challenge (5–40 (prime) and 10–160 (prime–boost)), whereas no virus-specific neutralizing antibodies were detected in control animals. IgM antibodies were present in the serum after vaccination on the day of the challenge in six out of six prime–boost and two out of six prime-only animals. SARS-CoV-2 spike-specific T cell responses were detected on the day of challenge. No statistically significant difference in the magnitude of the response was found between the prime–boost and prime-only group. Vaccination with ChAdOx1 nCoV-19 resulted in the induction of neutralizing antibodies against the vaccine vector itself within 28 days of vaccination. A boost vaccination with ChAdOx1 nCoV-19 resulted in a significant increase in binding and neutralizing antibodies in NHPs and an increase in the SARS-CoV-2 virus-neutralizing titre was not significantly correlated with the ChAdOx1 virus-neutralizing titre. (van et al., 2020) Six animals per group were vaccinated using a prime-only regimen (28 days before challenge) or a prime–boost regimen (56 and 28 days before challenge) intramuscularly with 2.5 × 1010 ChAdOx1 nCoV-19 virus particles each. As a control, six animals were vaccinated via the same route with the same dose of ChAdOx1 GFP. (van et al., 2020) Viral gRNA and sgRNA were detected in only two vaccinated animals on 3 d.p.i., and the viral load was significantly lower. Viral gRNA was detected in nose swabs from all animals and no difference was found on any day between vaccinated and control animals. Viral sgRNA was detected in a minority of samples, with no difference between groups. Infectious virus could only be detected at 1 and 3 d.p.i. in prime-only vaccinated and control animals, and 1 d.p.i. in prime–boost vaccinated animals. (van et al., 2020) No adverse events were observed after vaccination. (van et al., 2020) Rhesus macaques were challenged with a 50% tissue culture infective dose (TCID50) of 2.6 × 106 of SARS-CoV-2 in both the upper and lower respiratory tracts. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). (Folegatti et al., 2020) Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. (Folegatti et al., 2020) Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. (Folegatti et al., 2020) PIKA Recombinant COVID-19 Vaccine Yisheng Biopharma VO_0005345 Subunit vaccine Licensed Intramuscular injection (i.m.) Intramuscular injection (i.m.) Prime-2-CoV_Beta Speransa Therapeutics VO_0005400 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) PTX-COVID19-B Providence Therapeutics VO_0005236 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) QazCoVac-P Research Institute for Biological Safety Problems VO_0005273 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) QazVac QazCovid-in Research Institute for Biological Safety Problems, National Scientific Center for Phthisiopulmonology of the Republic of Kazakhstan VO_0005093 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Razi Cov Pars Razi Vaccine and Serum Research Institute VO_0005226 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) RBD-HBsAg VLP Serum Institute of India, Accelegen Pty VO_0005094 Virus Like Particle Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Recombinant SARS-CoV-2 vaccine (Sf9 cell) West China Hospital, Sichuan University VO_0005095 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) ReCOV Jiangsu Rec-Biotechnology VO_0005252 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Recombinant two-component spike and RBD protein (CHO cell) RH109 Wuhan Recogen Biotechnology Co., Ltd. VO_0005401 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) RQ3013 Walvax Biotechnology, Shanghai RNACure Biopharma VO_0005402 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) RVM-V001 RVAC Medicines RNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) S-268019 Shionogi VO_0005096 Subunit vaccine Clinical trial Intramuscular injection (i.m.) The vaccine S-268019-b is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-protein vaccine consisting of full-length recombinant SARS-CoV-2 S-protein (S-910823) as antigen, mixed with the squalene-based adjuvant A-910823 (Hashimoto et al., 2022) Intramuscular injection (i.m.) Two weeks after the second dosing, dose-dependent humoral immune responses were observed with neutralizing antibody titers being comparable to that of human convalescent plasma. (Hashimoto et al., 2022) No adverse clinical signs or weight loss associated with the vaccine were observed, suggesting safety of the vaccine in cynomolgus monkeys. SARS-CoV-2 Vaccine YF-S0 Live, attenuated vaccine Research YF17D [Ref5972:Sanchez-Felipe et al., 2021] Intraperitoneal injection (i.p.) A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine protects hamsters against SARS-CoV-2 challenge. (Sanchez-Felipe et al., 2021) Using an advanced reverse genetics system, a panel of YF17D-based candidate vaccines (YF-S) that express the S protein of SARS-CoV-2 in its noncleavable S0 version was generated. Intraperitoneal injection (i.p.) S protein of SARS-CoV-2 (Sanchez-Felipe et al., 2021) Recombinant vector construction (Sanchez-Felipe et al., 2021) At day 21, all hamsters vaccinated with YF-S1/2 and YF-S0 had seroconverted to high levels of S-specific IgG and virus NAbs with log10-transformed geometric mean titres for YF-S0 of 3.5 (95% confidence interval of 3.3–3.8) for IgG and 2.2 (95% confidence interval of 1.9–2.6) for NAbs, with rapid seroconversion kinetics. (Sanchez-Felipe et al., 2021) Hamsters were vaccinated at day 0 with a low dose of 10^3 PFU (via the intraperitoneal route) of the different constructs or YF17D and sham (as negative controls), and boosted after 7 days. (Sanchez-Felipe et al., 2021) Four days after infection, we detected high viral loads in the lungs of sham-vaccinated controls and hamsters vaccinated with YF17D as a matched placebo. Hamsters vaccinated with YF-S0 were protected against this aggressive challenge, with a median reduction of 5 log10-transformed viral RNA loads (interquartile range (IQR) of 4.5–5.4) in viral RNA loads, and of 5.3 log10-transformed virus titre (IQR of 3.9–6.3) for infectious virus in the lungs as compared to sham. (Sanchez-Felipe et al., 2021) After 23 or 28 days, hamsters were challenged intranasally with 2 × 10^5 PFU of SARS-CoV-2. (Sanchez-Felipe et al., 2021) SARS-CoV-2 VLP Vaccine The Scientific and Technological Research Council of Turkey VO_0005251 Virus like particle Clinical trial subcutaneous injection subcutaneous injection SC-Ad6-1 Tetherex Pharmaceuticals Corporation VO_0005254 Recombinant vector vaccine Clinical trial Adneviral vector Intramuscular injection (i.m.) Intramuscular injection (i.m.) SCB-2019 Clover Biopharmaceuticals, GSK, Dynavax VO_0004994 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) . SCB-2019 with no adjuvant elicited minimal immune responses (three seroconversions by day 50), but SCB-2019 with fixed doses of either AS03 or CpG/Alum adjuvants induced high titres and seroconversion rates of binding and neutralising antibodies in both younger and older adults (Richmond et al., 2021) Most local adverse events were mild injection-site pain (Richmond et al., 2021) SCB-2020S Clover Biopharmaceuticals AUS Pty Ltd VO_0005315 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) SCTV01C Sinocelltech Ltd. VO_0005338 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) SII B.1.351 Novavax VO_0005333 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) SII B.1.617.2 Novavax VO_0005335 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) SII Bivalent Novavax VO_0005334 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) SKYCovione SK Bioscience Co., Ltd. VO_0005197 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Soberana 02 FINLAY-FR-2 Instituto Finlay de Vacunas VO_0005097 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Soberana Plus Instituto Finlay de Vacunas VO_0005244 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) SpFN Walter Reed Army Institute of Research VO_0005237 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Sputnik V Gam-COVID-Vac VO_0005163 Recombinant vector vaccine Clinical trial recombinant adenovirus 26 and recombinant adenovirus 5 [Ref5458:Logunov et al., 2020] Intramuscular injection (i.m.) A SARS-CoV-2 recombinant viral vector vaccine composed of Ad26 and Ad5 vectors expressing S protein that lyophilised (Logunov et al., 2020). Intramuscular injection (i.m.) spike (S) protein (Logunov et al., 2020) SYS6006 CSPC ZhongQi Pharmaceutical Technology Co., Ltd. VO_0005410 mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Two rounds of immunization with SYS6006 were able to induce the neutralizing antibodies against the SARS-CoV-2 wild-type (WT) strain, and Delta and Omicron BA.2 variants in mice or non-human primates (NHPs). A3rd round of vaccination could further enhance the titers of neutralization against Delta and Omicron variants. (Xu et al., 2023) Turkovac ERUCOV-VAC Erciyes University VO_0005188 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) UB-612 Vaxxinity VO_0004995 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) Based on the receptor-binding domain protein binding antibody responses, the UB-612 third-dose booster may lead to an estimated approximately 95% efficacy against symptomatic COVID-19 caused by the ancestral strain.(Guirakhoo et. al 2022) UNAIR Inactivated COVID-19 Vaccine Airlangga University VO_0005411 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) V-01 Livzon Mabpharm Inc. VO_0005247 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) A dramatic increase (11.3-fold; 128.3-1452.8) of neutralizing titres was measured in the V-01 group at 14 days after the booster. Over two months of surveillance, vaccine efficacy was 47.8% (95%CI: 22.6-64.7) according to the intention-to-treat principle. (Wang et al. 2022) The most common adverse events were transient, mild-to-moderate pain at the injection site, fever, headache, and fatigue. (Wang et al. 2022) V-01-351/V-01D Bivalence Vaccine Livzon Pharmaceutical Group Inc. VO_0005412 Subunit vaccine Licensed Intramuscular injection (i.m.) Intramuscular injection (i.m.) In particular, V-01D-351 booster showed the highest pseudovirus neutralizing antibody titers against prototype SARS-CoV-2, Delta and Omicron BA.1 strains at day 14 post boosting, with GMTs 22.7, 18.3, 14.3 times higher than ICV booster, 6.2, 6.1, 3.8 times higher than V-01 booster (10 μg), and 5.2, 3.8, 3.5 times higher than V-01 booster (25 μg), respectively (Zhang et al., 2022). VAT00002 CoV2 preS dTM Sanofi Pasteur, GSK VO_0005085 Subunit vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) VB10.2129 Vaccibody AS VO_0005340 DNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) VB10.2210 Vaccibody AS VO_0005341 DNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) VBI-2902a VBI Vaccines Inc. VO_0005238 Virus Like Particle Clinical trial Intramuscular injection (i.m.) Aluminum phosphate (NCT04773665) Intramuscular injection (i.m.) SARS-CoV-2 spike glycoprotein (S protein) (NCT04773665) Antibody binding and neutralization titers were undiminished for more than 3 months after a single immunization. A single dose of this candidate, named VBI-2902a, protected Syrian golden hamsters from challenge with SARS-CoV-2 and supports the on-going clinical evaluation of VBI-2902a as a highly potent vaccine against COVID-19. (Fluckiger et al., 2021) VLA2001 Valneva, National Institute for Health Research (United Kingdom) VO_0005099 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) VLPCOV-01 VLP Therapeutics Japan GK mRNA vaccine Clinical trial Intramuscular injection (i.m.) Intramuscular injection (i.m.) VXA-CoV2-1 Vaxart VO_0005196 Recombinant vector vaccine Clinical trial Oral Oral Hamsters administered 2 doses of VXA-CoV2-1 showed a reduction in weight loss and lung pathology and had completely eliminated infectious virus 5 days postchallenge. Oral immunization induced antispike immunoglobulin G, and neutralizing antibodies were induced upon oral immunization with the sera, demonstrating neutralizing activity. (Johnson et al., 2022) Overall, these data demonstrate the ability of oral vaccine candidate VXA-CoV2-1 to provide protection against SARS-CoV-2 disease. (Johnson et al., 2022) VXS-1223 Vaxxas Pty Ltd VO_0005404 Subunit vaccine Clinical trial Intradermal injection (i.d.) Intradermal injection (i.d.) WIBP-CorV Wuhan Institute of Biological Products VO_0005160 Inactivated or "killed" vaccine Clinical trial Intramuscular injection (i.m.) An investigational inactivated whole-virus COVID-19 vaccine (Xia et al., 2020) Intramuscular injection (i.m.) whole virus (Xia et al., 2020) ZF2001 RBD-Dimer VO_0005142 Subunit vaccine Clinical trial Intramuscular injection (i.m.) A SARS-CoV-2 vaccine made of an SARS-CoV-2 RBD-sc-dimer (Dai et al., 2020) Intramuscular injection (i.m.) Induced neutralizing antibodies, production of RBD-Specific antibodies ((Zha, et al., 2020)) Balb/c Mice were immunized by subcutaneous injection with 50 μg of RBD-CuMVTT ((Zha, et al., 2020)) ZyCoV-D Zydus Cadila VO_0005162 DNA vaccine Clinical trial DNA plasmid [Ref5457:Kaur and Gupta, 2020] Intramuscular injection (i.m.) A SARS-CoV2 plasmid DNA vaccine that encodes the envelope protein (Kaur and Gupta, 2020). Intramuscular injection (i.m.) envelope protein (Kaur and Gupta, 2020) spike (S) protein Severe acute respiratory syndrome coronavirus 2 PR_P0DTC2 43740568 1796318598 GU280_gp02 LC528232 YP_009724390 2697049 21562 25383 + surface glycoprotein 6.62 131552.24 1273 Also known as spike glycoproteinstructural protein; spike protein >NC_045512.2:21562-25383 Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome AATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAA TTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAG TTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGT CTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCT TCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCC TACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATT TTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCG AATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCA AAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTAT TAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATT AACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAG GTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAA TGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAACAAAGTGTACGTTG AAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTG TTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGT TTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCA TTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATG CAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGA TTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCT AAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAG ATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTT TCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTT TCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACA AATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCT GCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAG ATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACC AGGTTGCTGTTCTTTATCAGGATGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTAC TCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCT GAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTC AGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGG TGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACC ACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAA CTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAAT AGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCA ATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCAT TTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTG CCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCT TTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGA CCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGG AGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAA ATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCAC AAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATAT CCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGT TTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTA CTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTAT GTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAG AACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTT CAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACAC ATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCT GAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAG GTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGC CAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCA TGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTA TGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGA CTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATA >YP_009724390.1 surface glycoprotein [Severe acute respiratory syndrome coronavirus 2] MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHV SGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPF LGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPI NLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYN ENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASV YAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYF PLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFL PFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLT PTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLG AENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGI AVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIG VTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDI LSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLM SFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNT FVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVA KNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD SEPVLKGVKLHYT Protective antigen ACTRN12620000674932 website 2020 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379861&isReview=true Agrati et. al 2021 journal Chiara Agrati , Stefania Capone , Concetta Castilletti, Eleonora Cimini, Giulia Matusali, Silvia Meschi, Eleonora Tartaglia, Roberto Camerini, Simone Lanini, Stefano Milleri, Stefano Colloca, Alessandra Vitelli, Antonella Folgori https://pubmed.ncbi.nlm.nih.gov/34737309/ Ahn et. al 2022 journal Jin Young Ahn, Jeongsoo Lee, You Suk Suh, Young Goo Song, Yoon-Jeong Choi, Kyoung Hwa Lee, Sang Hwan Seo, Manki Song, Jong-Won Oh, Minwoo Kim, Han Yeong Seo, Jeong-Eun Kwak, Jin Won Youn, Jung Won Woo, Eui-Cheol Shin, Young Chul Sung, Su-Hyung Park, Jun Yong Choi 2022 https://pubmed.ncbi.nlm.nih.gov/35156068 Ali et al., 2021 journal Kashif Ali 1, Gary Berman 1, Honghong Zhou 1, Weiping Deng 1, Veronica Faughnan 1, Maria Coronado-Voges 1, Baoyu Ding 1, Jacqueline Dooley 1, Bethany Girard 1, William Hillebrand 1, Rolando Pajon 1, Jacqueline M Miller 1, Brett Leav 1, Roderick McPhee 1 2021 https://pubmed.ncbi.nlm.nih.gov/34379915/ Anderson et al., 2020 journal Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, 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