Human Respiratory Syncytial Virus 11250 Respiratory tract disease Human Respiratory Syncytial Virus consists of two antigenic subtypes, A and B. Subtype B is more common and is considered the asymptomatic strain. More severe outbreaks are attributed to subtype A. The severity of the disease ranges from mild to life-threatening. It can cause mortality or morbidity in the elderly or immunosuppressed individuals. It is the most common pathogen leading to hospitalization in young children (Wiki: Human respiratory syncytial virus). 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 (rBCG-N-hRSV) Recombinant Mycobacterium bovis BCG vaccine rBCG-N-hRSV IDT Biologika Recombinant vector vaccine Clinical trial [Ref5665:Abarca et al., 2020] Bacillus Calmette-Guerin-Gudrun (BCG) is used as a vector. Intradermal injection (i.d.) Pontifcia Universidad Catholics de Chile (Abarca et al., 2020) rBCG-N-hRSV is a live attenuated recombinant Mycobacterium bovis BCG based on the Danish strain 1331 that expresses the nucleoprotein (N) of RSV (rBCG-N-hRSV)(BCG) that expresses the nuclei protein (N) of RSV. 0.05 mL of a reconstituted vial (2-8*10^6 CFU of the bacteria per 0.1 mL) of this vaccine is administered. This results in 1-4*10^5 CFU to a newborn. Intradermal injection (i.d.) (Abarca et al., 2020) N protein (Abarca et al., 2020) Both immunogenicity and reactogenicity responses were lower in BCG-WT immunized volunteers as compared to volunteers immunized with the study vaccine. N-RSV immune responses increased with higher doses of the vaccine Danish strain In each cohort, participants were vaccinated with 0.1 mL of the vaccine, as follows: 6 volunteers in Cohort A were vaccinated with the lowest dose (5 × 10^3 CFU); 6 volunteers in Cohort B received the middle dose (5 × 10^4 CFU); 6 volunteers in Cohort C received the highest dose (1 × 10^5 CFU) of the study vaccine. Each cohort included two volunteers vaccinated with 0.1 mL of the standard BCG vaccine (BCG-WT; a full dose of 1-33 × 10^5 CFU). (Abarca et al., 2020) rBCG-N-hRSV vaccine candidate was safe, well tolerated, and immunogenicity in healthy male adult volunteers. Both immunogenicity and reactogenicity responses were lower in control group as compared to volunteers immunized with the study vaccine. Individuals did not show enhancement of RSV disease. (Abarca et al., 2020) General (systemic) solicited AEs included fever, tachycardia, hypo/hypertension, headache, fatigue, myalgia, nausea/vomiting, and diarrhea. The findings with rBCG-N-hRSV vaccine are consistent with previous studies that showed that it induces a Th-1 RSV-specific immune response in mice, which was protective against RSV challenge Ad26/protein preF RSV Vaccine Coadministered With an Influenza Vaccine Fluarix Janssen (Leiden, the Netherlands) Other Licensed [Ref5639:Sadoff et al., 2021]An adenovirus serotype 26 (Ad26) vector Intramuscular injection (i.m.) (Sadoff et al., 2021) The vaccine Ad26.RSV.preF is the next-generation vaccine expressing the stabilized FA2. The vaccine is a replication-incompetent Ad26 vector containing a DNA transgene, encoding a F protein derived from the RSV A2 strain that is stabilized in its pre-F conformation (Sadoff et al., 2021) Each 0.5-mL dose contained 1 × 1011 viral particles (vp) of Ad26.RSV.preF. Fluarix Quadrivalent (GlaxoSmithKline), formulated for the 2017–2018 Northern Hemisphere season, contained the following 4 virus strains (15 μg of hemagglutinin per strain per 0.5-mL dose): A/Singapore/GP1908/2015 (H1N1) IVR-180, A/Hong Kong/4801/2014 (H3N2) NYMC X-263B, B/Phuket/3073/2013, and B/Brisbane/60/2008. The placebo was sterile 0.9% saline. Intramuscular injection (i.m.) 4 virus strains (15 μg of hemagglutinin per strain per 0.5-mL dose): A/Singapore/GP1908/2015 (H1N1) IVR-180, A/Hong Kong/4801/2014 (H3N2) NYMC X-263B, B/Phuket/3073/2013, and B/Brisbane/60/2008. The placebo was sterile 0.9% saline. In this phase 2a, double-blind, placebo-controlled study, 180 adults aged ≥60 years received Ad26.RSV.preF plus Fluarix on day 1 and placebo on day 29, or placebo plus Fluarix on day 1 and Ad26.RSV.preF on day 29 (control). Reported systemic reactogenicity and those graded 3 were generally more frequent after dosing with Ad26.RSV.preF than with Fluarix alone. Systemic reactogenicity was also higher after vaccination with Ad26.RSV.preF alone and in combination with Fluarix in this study than after vaccination with Ad26.RSV.preF alone, as previously reported in study VAC18193RSV1003 for a similar age group. Ad26.RSVpreF was generally well tolerated and had an acceptable safety profile(Sadoff et al., 2021) (Sadoff et al., 2021) Adenoviral vectors adenovirus serotypes 26 and 35 (Ad26 and Ad35), expressing the nonstabilized form of the F protein of the RSV strain A2 induced strong RSV specific humoral and cellular immune responses in mice and were protective in the cotton rat challenge model. Ad26 vectors encoding the RSV F glycoprotein, the most immunogenic antigen in a RSV vaccine [24, 26, 28], have demonstrated high and durable RSV neutralizing antibody titers, a T-helper 1–type cellular immune response and protective immunity in an animal challenge model Ad5-RSV-F Recombinant vector vaccine Research Intramuscular injection (i.m.) Adenovirus serotype 5-based RSV vaccine encoding the fusion (F) protein (Ad5.RSV-F)(Kim et al., 2014) Intramuscular injection (i.m.) Animals were immunized intranasally (i.n.) and/or intramuscularly (i.m.) with Ad5.RSV-F (Kim et al., 2014) (Kim et al., 2014)The vaccine provided protective immunity against RSV challenge without enhanced lung disease in the rats (Kim et al., 2014)Post vaccination, animals were subsequently challenged with RSV/A/Tracy (i.n.) D46/NS2/N/ΔM2-2-HindIII Charles river Laboratories Live, attenuated vaccine Licensed intranasal immunization (McFarland et al., 2020)The vaccine, D46/NS2/N/ΔM2-2-HindIII, is a cDNA-derived version of RSV subgroup A, strain A2. In addition, D46/NS2/N/ΔM2-2-HindIII has the MEDI/ΔM2-2 assignments at the only 2 amino acid positions that differ between MEDI/ΔM2-2 and LID/ΔM2-2. D46/NS2/N/ΔM2-2-HindIII contains the complete 112-nucleotide 3’ noncoding region of the SH gene that is present in biological RSV A2 but was deleted in LID/ΔM2-2. D46/NS2/N/ΔM2-2-HindIII was recovered from cDNA in qualified Vero cells. intranasal immunization Deletion (McFarland et al., 2020)The vaccine uses backbone of LId/M2-2 vaccine but has a 234 nucleotide M2-2 deletion with the same structure as in MEDI/m2-2 he study included children ≥6 and <25 months of age who were healthy, had no current or past lung disease, and were RSV seronegative at screening (McFarland et al., 2020) (McFarland et al., 2020) When administered to RSV-naive 6–24 month-old infants and children, the RSV D46/NS2/N/ΔM2-2-HindIII candidate vaccine was well tolerated, was highly infectious (100% of participants had evidence of vaccine shedding and/or a serum RSV antibody response), and resulted in excellent induction of serum RSV-specific antibodies, including neutralizing antibodies. During the 28 days after inoculation, mild upper respiratory tract and/or febrile events occurred in both vaccine and placebo recipients, with 76%. All respiratory symptoms in both groups were grade 1. Grade 2 fever occurred in 1 vaccinee and 1 placebo recipient. Of the 16 vaccinees with respiratory or febrile illness, illness was concurrent with vaccine alone detected in NW specimens in 12, vaccine plus rhinovirus in 2, vaccine plus rhinovirus and adenovirus in 1, and parainfluenza type 4 and no vaccine virus in 1. (McFarland et al., 2020) (McFarland et al., 2020)The D46/NS2/N/ΔM2-2-HindIII vaccine had excellent infectivity and generated robust neutralizing antibody and anti-RSV F protein IgG responses. HDAd-sFsyn VO_0004802 Recombinant vector vaccine Research Intramuscular injection (i.m.) (Fu et al., 2014) Intramuscular injection (i.m.) HRSV DNA vaccine DRF-412 VO_0004579 DNA vaccine Research phCMV1 [Ref2711:Wu et al., 2009] Intramuscular injection (i.m.) the ctxA(2)B region of the cholera toxin gene (Wu et al., 2009) Intramuscular injection (i.m.) DNA vaccine construction The DRF-412 vaccine vector was as effective as live RSV in inducing neutralization antibody, systemic Ab (IgG, IgG1, IgG2a, and IgG2b) responses, and mucosal antibody responses (Ig A). Mice inoculated with vector DRF-412 induced a higher mixed Th1/Th2 cytokine immune response than DRF-412-P (Wu et al., 2009). VO_0003057 Mice immunized with DRF-412 and DRF-412-P have a higher average Ct value compared with PBS and phCMV I group (P < 0.001), which means that they have less viral mRNA in the lung indicating better protection, but there was no statistically significant difference between DRF-412 and DRF-412-P. This vaccine induced partial protection against RSV in mice (Wu et al., 2009). HRSV DNA vaccine pND-G VO_0004580 DNA vaccine Research pND [Ref2714:Miller et al., 2002] Intradermal injection (i.d.) Intradermal injection (i.d.) DNA vaccine construction VO_0003057 Immunization with the pND-G vaccine significantly inhibited the RSV induced increase in airway responsiveness to methacholine (Mch) (n=3 separate experiments; 12 mice per group) (P<0.05 versus RSV). The concentration of Mch required to induce a 200% increase in airway responsiveness (PC200) was significantly greater in RSV infected mice who had received the pND-G vaccine compared to RSV infected mice who had not received the vaccine (21.5 mg/ml Mch versus 7.2 mg/ml Mch) (P<0.05) (Miller et al., 2002). Human Respiratory Syncytial Virus M2-2 mutant vaccine VO_0002978 Live, attenuated vaccine Research intranasal immunization intranasal immunization Gene mutation This M2-2 is from Human Respiratory Syncytial Virus (Jin et al., 2003). An M2-2 mutant is attenuated in African green monkeys (Jin et al., 2003). An M2-2 mutant induces significant protection in African green monkeys from challenge with wild type HRSV (Jin et al., 2003). licensed Respiratory syncytial virus infection human vaccine Generic Unknown VO_0002512 Inactivated or "killed" vaccine Licensed A generic representation of vaccines developed to prevent respiratory tract disease caused by respiratory syncytial virus (RSV) in humans, utilizing inactivated or 'killed' virus preparations. These vaccines aim to induce immunity without causing disease by using virus particles that have been rendered non-infectious. LID/ΔM2-2/1030s Charles River Laboratories Malvern, PA Live, attenuated vaccine Clinical trial Intramuscular injection (i.m.) The vaccine, LID/ΔM2-2/1030s, is a cDNA-derived version of RSV subgroup A, strain A2 with 241 nts deleted from the M2-2 ORF and the 3 potential translation initiation codons of the M2-2 ORF silenced (McFarland et al., 2020). Intramuscular injection (i.m.) Recombinant protein preparation 241 deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 (McFarland et al., 2020). (McFarland et al., 2020)Eligible children were RSV seronegative at screening, defined as having a complement-enhanced serum RSV 60% plaque reduction neutralizing titer. Respiratory syncytial virus-seronegative children ages 6–24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. (McFarland et al., 2020)Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. (McFarland et al., 2020)The small sample size precludes firm estimates of rates of vaccine-associated events, infectivity, immunogenicity, and viral replication. The vaccine, LID/ΔM2-2/1030s, is a cDNA-derived version of RSV subgroup A, strain A2. The results showed that the LID/∆M2-2/1030s is a very attractive candidate for further development as a live attenuated in trans Al pediatric RSV vaccine. MEDI-534 MedImmune LLC Recombinant vector vaccine Clinical trial Consists of the bovine parainfluenza virus type 3 (PIV3). intranasal immunization MEDI 534 is a live attenuated type 3 vectored RSV vaccine intransally administered and engineered to express RSV F, neutralizing antibodies against both RSV A and B subtypes.(Yang et al., 2013) The bovine parainfluenza virus type 3 (PIV3) genome was substituted with human PIV3 F and HN glycoproteins engineered to express RSV F protein.(Yang et al., 2013) intranasal immunization Recombinant protein preparation Bovine parainfluenza virus type 3 genome was substituted with HN glycoproteins.(Yang et al., 2013) Recombinant protein preparation Substituting the human PIV3 F and HN glycoproteins to express RSV F protein (Yang et al., 2013). Mnull RSV Live, attenuated vaccine Clinical trial intranasal immunization Mnull RSV is derived from a human RSV A2 strain. The gene for the RSV M protein has been deleted. Mnull RSV is grown in HEp-2 respiratory epithelial cells transfected to express the viral M protein. The vaccine virus is fully infectious, and synthesizes all of its proteins (except M) after entering HEp-2 cells (Ivanov et al., 2021). RSV M protein was deleted (Ivanov et al., 2021). intranasal immunization Fusion (F) protein Recombinant protein preparation Deletion of RSV M protein. (Ivanov et al., 2021) MVA - RSV Bavarian Nordic Recombinant vector vaccine Licensed [Ref5613:Endt et al., 2022]This vaccine is based on the attenuated virus Vector, modified Vaccinia Ankara Bavarian Nordic, encoding the RSV fusion protein (F), glycoprotein (G), nuclei protein (N), and transcription elongation factor derived from RSV subtype A, as well as another G of RSV subtype B. intranasal immunization (Endt et al., 2022)The MVA RSV contains five SV specific antigens that induced antibody and T cell responses which is currently being tested in the clinical trials for people older than 55 years of age. Depletion of CD4 or CD8 T cells, serum transfer, and the use of genetically engineered mice lacking the ability to generate either RSV-specific antibodies, the IgA isotope, or CD8 T cells revealed that complete protection from RSV infection is dependent on CD4 and CD8 T cells as well as antibodies, including IgA. MVA-RSV vaccination optimally protects against RSV infection by employing multiple arms of the adaptive immune system. (Endt et al., 2022) Production was conducted in roller bottles seeded with primary CEF cells under serum-free conditions. Infected CEF lysates were sonicated, purified, and concentrated using a standardized two-step sucrose cushion centrifugation procedure. Vaccine infectious titer, sequence identity, and integrity were confirmed. (Endt et al., 2022)MVA-RSV was generated by homologous recombination. Primary Chicken embryo fibroblast cells were infected with MVA -BN and transferred with recombination plasmids. During homologous recombination, sequences within the plasmid homologous to the insertion sites of the MVA - BN genome recombine with their corresponding sequences within the viral genome and target the trans genes into the respective integration site of MVA - BN. MVA-RSV was further propagated in CEF cells at serum-free conditions. After insertion of the antigens into the MVA-BN genome, genetically pure clones were isolated by repeated rounds of limiting dilution and plaque purification. were isolated by repeated rounds of limiting dilution and plaque purification. A final clone was amplified, and a stock was prepared. intranasal immunization (Endt et al., 2022) RSV fusion protein (F), glycoprotein (G), nucleoprotein (N), transcription elongation factor from RSV A, and glycoprotein from RSV strain B. (Endt et al., 2022)IgA deficient mice at the age of 12 to 24 weeks, CD8 deficient mice the insertion sites of the MVA - BN genome recombine with their corresponding sequences within the viral genome and target the trans genes into the respective integration site of MVA - BN. Mice were administered intranasally (IN) with 100 μl of the MVA-RSV vaccine at 1 × 108 TCID50 per dose at Days 0 and 21. IN challenge was performed with 100 μl of RSV-A2 at 1 × 106 pfu at Day 35 (9, 15). Control animals received TRIS-buffered saline, pH 7.7. For IN applications, mice were anesthetized with a mixture of Fentanyl, Midazolam, and Medetomidine and anesthesia was antagonized with a mixture of Naloxone, Flumazenil, and Atipamezole. After challenge, animals were monitored daily, and body weight was measured. Animals were sacrificed 4 days post challenge. (Endt et al., 2022) MSV - RSV induced both broad T cell responses against all encoded RSV antigens and humoral responses against RSV A and RSV B. These results suggest that MVA - RSV may activate various adaptive immune responses against RSV that could contribute to different pathways of protection. (Endt et al., 2022)After vaccination with MVA-RSV, clearance of RSV from murine lungs was only complete in the presence of RSV-specific antibodies, including mucosal IgA, as well as CD4 and CD8 T cells. MVA-RSV induces immune parameters from all arms of the adaptive immune system, which together warrant sterilizing protection against RSV exposure. rB-HPIV3-F1 Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Virus expressing the RSV F ORF (rB/HPIV3-F1)(Schmidt et al., 2001) Intramuscular injection (i.m.) rB-HPIV3-G1 Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Recombinant PIV3 expressing the RSV G ORF (Schmidt et al., 2001) Intramuscular injection (i.m.) rB/HPIV3- RSV-F Recombinant vector vaccine Research Intramuscular injection (i.m.) rB/HPIV3 viruses expressing RSV F from the first (pre-N), second (N-P), third (P-M), and sixth (HN-L) genome positions (Liang et al., 2014), Intramuscular injection (i.m.) Recombinant vector construction RSV F from the first (pre-N), second (N-P), third (P-M), and sixth (HN-L) genome positions is expressed in a recombinant vaccine vector rB/HPIV3 viruses (Liang et al., 2014). The hamsters were inoculated intranasally with 0.1 ml containing 10^6 TCID50 of rB/HPIV3-RSV F virus or with 10*6 PFU of wt RSV (A2 strain) (Liang et al., 2014) . Each rB/HPIV3 vector induced a high titer of neutralizing antibodies in hamsters against RSV and HPIV3. Protection against RSV challenge was greater for position 2 than for position 6. Evaluation of insert stability suggested that RSV F is under selective pressure to be silenced during vector replication in vivo, but this was not exacerbated by a high level of RSV F expression and generally involved a small percentage of recovered vector (Liang et al., 2014) Challenge was performed by intranasal infection with 106 PFU of RSV in 0.1 ml at 31 days after immunization(Liang et al., 2014) rBPIV3-RSV-G Recombinant vector vaccine Research Intramuscular injection (i.m.) bPIV3 as a virus vaccine vector with the introduction of the RSV attachment (G) and fusion (F) genes into the bPIV3 RNA genome(Haller et al., 2003) Intramuscular injection (i.m.) G and F protein (Falsey et al., 2022) Recombinant vector construction Hamsters were infected intranasally with 1×106  p.f.u. r-bPIV3, bPIV3/RSV(I), RSV or placebo (Opti-MEM) in a 0·1 ml volume(Haller et al., 2003) The recombinant virus expressed the RSV G and F proteins sufficiently to evoke a protective immune response in hamsters upon challenge with RSV or human PIV3 and to elicit RSV neutralizing and PIV3 haemagglutinin inhibition serum antibodies. In effect, a bivalent vaccine was produced that could protect vaccinees from RSV as well as PIV3(Haller et al., 2003) Animals were inoculated on day 21 intranasally with 1×106 p.f.u. of hPIV3 or RSV. (Haller et al., 2003) Respiratory syncytal virus bivalent prefusion F vaccine Subunit vaccine Clinical trial Intramuscular injection (i.m.) A bivalent prefusion F vaccine (RSVpreF) containing trimeric F glycoproteins from both major RSV subgroups (A and B) engineered for stability in the prefusion conformation is in clinical development in adult (Falsey et al., 2022). (Falsey et al., 2022) Intramuscular injection (i.m.) F protein Recombinant protein preparation A trimeric F glycoproteins from both major RSV subgroups (A and B) engineered for stability in the prefusion conformation is in clinical development in adults (Falsey et al., 2022). Among older adults 65–85 years in the expanded cohort, RSV A 50% neutralizing GMTs in RSVpreF recipients increased from 1793–2734 before vaccination to 14 905–27 600 at 1 month postvaccination (Figure 3). RSV B neutralizing titers increased from 1635–2685 before vaccination to 15 169–30 071 at 1 month postvaccination. Postimmunization neutralizing titers were similarly high across RSVpreF dose levels and formulations; corresponding GMFRs were 7.2–13.2 for RSV A and 6.9–14.9 for RSV B across RSVpreF groups, and 1.1 for RSV A and 0.9 for RSV B for placebo recipients (findings were similar for older adults in the sentinel cohort. Patient was given a single 60-µg, 120-µg or 240-µg dose on day 0. 124/490 of participants in the RSVpreF cohorts had local reactions within 14 days post–vaccination. The majority (82.2% [102/124]) of participants who reported local reactions rated them mild in severity; pain at the injection site was the most common (22.2% [109/490]) (Falsey et al., 2022). rPIV3-RSV-hMPV Recombinant vector vaccine Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) Recombinant protein preparation The hamsters were vaccinated intranasally with 106 PFU of b/h PIV3, b/h PIV3/RSV, RSV A2, b/h PIV3/hMPV, hMPV/NL/1/00, or placebo medium in a 100-μl volume, (Tang et al., 2003) Animals immunized with b/h PIV3/RSV were protected completely from hPIV3 and RSV infection. (Tang et al., 2003) Animals were challenged intranasally with 106 PFU of RSV or hPIV3 per animal on day 28 postvaccination. (Tang et al., 2003) RSV/ΔNS2/Δ1313/I1314 Charles River Laboratories Live, attenuated vaccine Research Intramuscular injection (i.m.) (Karron et al., 2020)RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the RSV polymerase gene and the stabilizing missense mutation I1314L. (Karron et al., 2020)CTM was stored at −70°C and diluted to dose on site using Leibovitz L15 medium. Intramuscular injection (i.m.) Gene mutation (Karron et al., 2020)Has a 523 nucleotide deletion of the NS2 gene. RSV/ΔNS2/Δ1313/I1314L was derived from a recombinant version of wt RSV strain A2 with the further modification of a 112 nucleotide phenotypically silent deletion in the SH noncoding sequence that stabilizes the complementary DNA (cDNA) during propagation in bacteria. Codon deletion (Karron et al., 2020)A codon deletion in the L gene (Δ1313; deletion of S1313) plus the adjacent missense mutation I1314L that prevents the compensatory deattenuating mutation I1314T. RSV/ΔNS2/Δ1313/I1314L was derived from a recombinant version of wt RSV strain A2 with the further modification of a 112 nucleotide phenotypically silent deletion in the SH noncoding sequence that stabilizes the complementary DNA (cDNA) during propagation in bacteria. (Karron et al., 2020) Children were given a dose of 10^6 PFU and in RSV-seronegative children at a dose of 10^5 or 10^6 PFU (Figure 1). Children were randomized 2:1 to receive vaccine or placebo, administered as nose drops The vaccination showed statistically significant differences in log-fold plaque reduction neutralization antibody titers and the presence of 4-fold increase in RSV F IgG response in both seropositive and seronegative responses. However, 16/20 seropositive and 17/20 seronegative children in the placebo group did have RSV neutralizing antibody responses occured in 16 of 20 and F IgG responses in 17 of 20 RSV-seronegative children who received 106 PFU . For recipients of 105 and  106 PFU, the mean postvaccination PRNT was  1:37 and 1:64, respectively. (Karron et al., 2020) (Karron et al., 2020)In RSV-seropositive participants, URI was observed in 2 and cough was observed in 1 of 10 vaccinees during the 28-day postimmunization reporting period (Table 1); in each case, rhinovirus was detected in NW samples at the time of illness. None of the vaccinees shed vaccine virus, indicative of attenuation. rVSV-Gstem-RSV-F Recombinant vector vaccine Research Intramuscular injection (i.m.) Recombinant vesicular stomatitis virus (rVSV) replicon in which the attachment and fusion domains of the VSV glycoprotein (G) have been deleted (rVSV-Gstem)(Johnson et al., 2013) Intramuscular injection (i.m.) F protein (Johnson et al., 2013) Mice were immunized on day 0. In studies that included a boost, mice were boosted at week 4(Johnson et al., 2013) (Johnson et al., 2013) A single high dose of the Gstem-RSV-F replicon was effective against challenge with both RSV A and B subgroup viruses. Finally, addition of an RSV glycoprotein (G)-expressing Gstem vector significantly improved the incomplete protection achieved with a single low dose of Gstem-RSV-F vector alone RSV challenge virus was administered by the nasal route 4 weeks after the last immunization dose(Johnson et al., 2013) VSV-RSV(F/G) Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Recombinant vesicular stomatitis virus (rVSV) replicon in which the attachment and fusion domains of the VSV glycoprotein (G) have been deleted (rVSV-Gstem)(Johnson et al., 2013) Intramuscular injection (i.m.) Recombinant protein preparation Since Gstem lacks the receptor binding and fusion domains, needs the G protein in trans (Johnson et al., 2013). F protein Human respiratory syncytial virus 306438651 CDD:278924 GOA:E0WLR1 InterPro:IPR000776 UniProtKB/TrEMBL:E0WLR1 208893 ? F protein 10.23 18105.35 239 Fusion glycoprotein F0; pfam00523 >CBW45366.1 F protein, partial [Human respiratory syncytial virus A] MELPILKTNAITTIFAAVTLCFASSQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCN GTDAKVKLIKQELDKYKNAVTELQLLMQSTPAANNRARRELPRFMNYTLNNTKNNNVTLSKKRKRRFLGF LLGVGSAIASGIAVSKVLHLEGEVNK Protective antigen [Ref5687:Oomens et al., 2006]HRSV F protein CT plays a critical role in F protein cellular localization and production of infectious virus. HRSV F protein can induce membrane fusion in the absence of the homotypic attachment protein. G Human respiratory syncytial virus A strain Long 1353203 CDD:144411 CDD:224196 11260 ? Major surface glycoprotein G 10.72 34785.98 465 Attachment glycoprotein G; Membrane-bound glycoprotein; mG >sp|P20895.2|GLYC_HRSVL RecName: Full=Major surface glycoprotein G; AltName: Full=Attachment glycoprotein G; AltName: Full=Membrane-bound glycoprotein; Short=mG MSKNKDQRTAKTLEKTWDTLNHLLFISSGLYKLNLKSIAQITLSILAMIISTSLIITAIIFIASANHKVT LTTAIIQDATSQIKNTTPTYLTQDPQLGISFSNLSEITSQTTTILASTTPGVKSNLQPTTVKTKNTTTTQ TQPSKPTTKQRQNKPPNKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTFKT TKKDHKPQTTKPKEVPTTKPTEEPTINTTKTNIITTLLTNNTTGNPKLTSQMETFHSTSSEGNLSPSQVS TTSEHPSQPSSPPNTTRQ Protective antigen [Ref5688:Tripp et al., 2018]The G protein modulates neonatal regulatory B lymphocytes (nBreg cells) to produce immunosuppressive interleukin-10 (IL-10). HN Human respirovirus 1 935266 19718372 Hpv1gp09 NP_604441 12730 6846 8739 + mRNA 7.96 61174.65 575 >NC_003461.1:6846-8739 Human parainfluenza virus 1, complete genome TAGGGTTAAAGACAATCCAGTCAACCTATAAGGCAACAGCATCCGATTATACAAACGATGGCTGAAAAAG GGAAAACAAATAGTTCATATTGGTCTACAACCCGAAATGACAATTCCACGGTAAACACACACATTAATAC ACCAGCAGGAAGGACACACATCTGGCTACTGATTGCAACAACAATGCATACAGTATTGTCCTTCATTATC ATGATCCTATGCATTGACCTAATTATAAAACAAGACACTTGTATGAAGACAAACATCATGACAGTATCCT CCATGAACGAAAGTGCCAAAATAATCAAAGAGACAATCACAGAATTAATCAGACAAGAAGTAATATCAAG GACCATAAACATACAAAGTTCAGTACAAAGCGGGATCCCAATATTGTTAAACAAGCAAAGCAGAGATCTC ACACAATTAATAGAGAAGTCATGCAACAGACAGGAATTGGCTCAGATATGCGAAAACACCATTGCTATTC ACCATGCAGACGGCATATCTCCTCTGGACCCACACGATTTCTGGAGATGTCCCGTAGGGGAACCCCTACT GAGCAACAACCCCAATATCTCATTATTACCTGGACCAAGTCTACTTTCTGGATCCACCACAATTTCAGGA TGTGTTAGACTACCTTCATTATCAATTGGTGATGCAATATATGCGTATTCATCAAACTTAATCACTCAAG GATGTGCAGATATAGGGAAGTCATATCAGGTTTTACAATTAGGTTACATATCCTTAAATTCAGATATGTA TCCTGATTTAAACCCGGTAATTTCTCATACCTATGACATCAACGACAACAGGAAATCATGTTCTGTAATA GCTGCAGGAACAAGGGGTTATCAGTTATGCTCCTTGCCCACTGTGAATGAGACTACAGACTACTCGAGTG AAGGTATAGAAGATTTAGTATTTGACATATTAGATCTCAAGGGAAAGACCAAATCTCATCGATACAAAAA TGAAGATATAACTTTTGACCATCCTTTTTCTGCAATGTATCCGAGTGTAGGAAGTGGGATAAAAATTGAA AATACACTCATTTTCCTAGGGTACGGTGGCTTAACAACTCCGCTCCAAGGCGACACTAAGTGTGTGATAA ACAGATGTACCAATGTTAATCAGAGTGTTTGCAATGATGCTCTTAAGATAACTTGGCTAAAGAAAAGACA AGTTGTCAATGTCTTAATTCGTATCAATAATTATTTATCTGATAGGCCAAAGATTGTTGTCGAGACAATT CCAATAACTCAAAATTACTTAGGTGCCGAAGGTAGGCTACTTAAACTAGGTAAAAAGATCTACATATATA CTAGATCTTCAGGTTGGCACTCCAACCTGCAAATAGGATCATTAGATATCAACAACCCCATGACCATTAA ATGGGCGCCTCATGAAGTCCTGTCTCGACCAGGAAACCAAGACTGCAACTGGTACAACAGATGTCCGAGA GAATGCATATCAGGTGTATATACTGATGCATATCCACTATCTCCTGATGCAGTCAATGTTGCTACAACCA CACTGTACGCAAACACATCACGTGTTAATCCCACCATAATGTACTCAAATACCTCAGAAATTATCAACAT GCTAAGACTCAAGAATGTACAACTAGAGGCAGCATACACTACTACATCATGTATCACTCATTTCGGGAAG GGCTACTGCTTCCACATTGTTGAAATCAACCAAGCCAGCCTTAATACCTTACAACCTATGTTGTTCAAGA CAAGTATCCCTAAAATATGTAAAATCACATCTTGAGCAGATCAAGACCCAACACTATATCAATTATGTGA AAACCAGATATGATGTATAAAAATTTAAAAACAAAGCATGAATAGACATTTATATGACAAATAGAATAAG AAAA >NP_604441.1 HN glycoprotein [Human respirovirus 1] MAEKGKTNSSYWSTTRNDNSTVNTHINTPAGRTHIWLLIATTMHTVLSFIIMILCIDLIIKQDTCMKTNI MTVSSMNESAKIIKETITELIRQEVISRTINIQSSVQSGIPILLNKQSRDLTQLIEKSCNRQELAQICEN TIAIHHADGISPLDPHDFWRCPVGEPLLSNNPNISLLPGPSLLSGSTTISGCVRLPSLSIGDAIYAYSSN LITQGCADIGKSYQVLQLGYISLNSDMYPDLNPVISHTYDINDNRKSCSVIAAGTRGYQLCSLPTVNETT DYSSEGIEDLVFDILDLKGKTKSHRYKNEDITFDHPFSAMYPSVGSGIKIENTLIFLGYGGLTTPLQGDT KCVINRCTNVNQSVCNDALKITWLKKRQVVNVLIRINNYLSDRPKIVVETIPITQNYLGAEGRLLKLGKK IYIYTRSSGWHSNLQIGSLDINNPMTIKWAPHEVLSRPGNQDCNWYNRCPRECISGVYTDAYPLSPDAVN VATTTLYANTSRVNPTIMYSNTSEIINMLRLKNVQLEAAYTTTSCITHFGKGYCFHIVEINQASLNTLQP MLFKTSIPKICKITS Protective antigen M protein AHB33452 11250 ? M 8.57 27189.22 256 subgroup: B; genotype: BA [Ref5686:Shahriari et al., 2018]The M protein is a non-glycosylated phosphorylated protein located external to the nucleocapsid layer, where it acts as a bridge between the lipid bilayer envelope and the nucleocapsid. >AHB33452.1 M [Human orthopneumovirus] METYVNKLHEGSTYTAAVQYNVLEKDDDPASLTIWVPMFQSSVPADLLIKELASINILVKQISTPKGPSL RVTINSRSAVLAQMPSNFTISANVSLDERSKLAYDVTTPCEIKACSLTCLKVKSMLTTVKDLTMKTFNPT HEIIALCEFENIMTSKRVIIPTYLRSISVKNKDLNSLENIATTEFKNAITNAKIIPYAGLVLVITVTDNK GAFKYIKPQSQFIVDLGAYLEKESIYYVTTNWKHTATRFSIKPLED Virmugen M2-2 Human respiratory syncytial virus A2 81925031 CDD:116003 11259 ? Matrix M2-2 90 Matrix M2-2. /FTId=PRO_0000356857. >gi|81925031|sp|P88812.1|M22_HRSVA RecName: Full=Matrix M2-2 MTMPKIMILPDKYPCSITSILITSRCRVTMYNQKNTLYFNQNNPNNHMYSPNQTFNEIHWTSQELIDTIQ NFLQHLGIIEDIYTIYILVS Virmugen An M2-2 mutant of human respiratory syncytial virus A2 is attenuated in African green monkeys. When challenged with wild type RSV, two doses provided complete protection against challenge in the lower respiratory tract and a significant reduction of the challenge virus in the upper respiratory tract [Ref1999:Jin et al., 2003]. Abarca et al., 2020 journal Abarca K, Rey-Jurado E, Muñoz-Durango N, Vázquez Y, Soto JA, Gálvez NMS, Valdés-Ferrada J, Iturriaga C, Urzúa M, Borzutzky A, Cerda J, Villarroel L, Madrid V, González PA, González-Aramundiz JV, Bueno SM, Kalergis AM 2020 27 100517 EClinicalMedicine Chatterjee et al., 2017 journal Chatterjee S, Luthra P, Esaulova E, Agapov E, Yen BC, Borek DM, Edwards MR, Mittal A, Jordan DS, Ramanan P, Moore ML, Pappu RV, Holtzman MJ, Artyomov MN, Basler CF, Amarasinghe GK, Leung DW 2017 2 17101 Nature microbiology Domachowske et al., 2018 journal Domachowske JB, Khan AA, Esser MT, Jensen K, Takas T, Villafana T, Dubovsky F, Griffin MP 2018 37 9 886-892 The Pediatric infectious disease journal Drachev et al., 1976 journal Drachev LA, Jasaitis AA, Mikelsaar H, Nemecek IB, Semenov AY, Semenova EG, Severina II, Skulachev VP 1976 251 22 7077-7082 The Journal of biological chemistry Endt et al., 2022 journal Endt K, Wollmann Y, Haug J, Bernig C, Feigl M, Heiseke A, Kalla M, Hochrein H, Suter M, Chaplin P, Volkmann A 2022 13 841471 Frontiers in immunology Eyles et al., 2013 journal Eyles JE, Johnson JE, Megati S, Roopchand V, Cockle PJ, Weeratna R, Makinen S, Brown TP, Lang S, Witko SE, Kotash CS, Li J, West K, Maldonado O, Falconer DJ, Lees C, Smith GJ, White P, Wright P, Loudon PT, Merson JR, Jansen KU, Sidhu MK 2013 208 2 319-329 The Journal of infectious diseases Falsey et al., 2022 journal Falsey AR, Walsh EE, Scott DA, Gurtman A, Zareba A, Jansen KU, Gruber WC, Dormitzer PR, Swanson KA, Jiang Q, Gomme E, Cooper D, Schmoele-Thoma B 2022 225 12 2056-2066 The Journal of infectious diseases Fu et al., 2014 journal Fu YH, Jiao YY, He JS, Giang GY, Zhang W, Yan YF, Ma Y, Hua Y, Zhang Y, Peng XL, Shi CX, Hong T 2014 105 72-79 Antiviral research Gan et al., 2012 journal Gan SW, Tan E, Lin X, Yu D, Wang J, Tan GM, Vararattanavech A, Yeo CY, Soon CH, Soong TW, Pervushin K, Torres J 2012 287 29 24671-24689 The Journal of biological chemistry Gilman et al., 2019 journal Gilman MSA, Furmanova-Hollenstein P, Pascual G, B van 't Wout A, Langedijk JPM, McLellan JS 2019 10 1 2105 Nature communications Haller et al., 2003 journal Haller AA, Mitiku M, MacPhail M 2003 84 Pt 8 2153-2162 The Journal of general virology Jin et al., 2003 journal Jin H, Cheng X, Traina-Dorge VL, Park HJ, Zhou H, Soike K, Kemble G 2003 21 25-26 3647-3652 Vaccine Johnson et al., 2013 journal Johnson JE, McNeil LK, Megati S, Witko SE, Roopchand VS, Obregon JH, Illenberger DM, Kotash CS, Nowak RM, Braunstein E, Yurgelonis I, Jansen KU, Kalyan NK, Sidhu MK 2013 150 1-2 134-144 Immunology letters Karron et al., 2020 journal Karron RA, Luongo C, Mateo JS, Wanionek K, Collins PL, Buchholz UJ 2020 222 1 82-91 The Journal of infectious diseases Kim et al., 2014 journal Kim E, Okada K, Beeler JA, Crim RL, Piedra PA, Gilbert BE, Gambotto A 2014 88 9 5100-5108 Journal of virology Liang et al., 2014 journal Liang B, Munir S, Amaro-Carambot E, Surman S, Mackow N, Yang L, Buchholz UJ, Collins PL, Schaap-Nutt A 2014 88 8 4237-4250 Journal of virology McFarland et al., 2020 journal McFarland EJ, Karron RA, Muresan P, Cunningham CK, Perlowski C, Libous J, Oliva J, Jean-Philippe P, Moye J, Schappell E, Barr E, Rexroad V, Fearn L, Cielo M, Wiznia A, Deville JG, Yang L, Luongo C, Collins PL, Buchholz UJ 2020 221 12 2050-2059 The Journal of infectious diseases McFarland et al., 2020 journal McFarland EJ, Karron RA, Muresan P, Cunningham CK, Libous J, Perlowski C, Thumar B, Gnanashanmugam D, Moye J, Schappell E, Barr E, Rexroad V, Fearn L, Spector SA, Aziz M, Cielo M, Beneri C, Wiznia A, Luongo C, Collins P, Buchholz UJ 2020 221 4 534-543 The Journal of infectious diseases Miller et al., 2002 journal Miller M, Cho JY, Baek KJ, Castaneda D, Nayar J, Rodriguez M, Roman M, Raz E, Broide DH 2002 20 23-24 3023-3033 Vaccine Oliveira et al., 2013 journal Oliveira AP, Simabuco FM, Tamura RE, Guerrero MC, Ribeiro PG, Libermann TA, Zerbini LF, Ventura AM 2013 177 1 108-112 Virus research Oomens et al., 2006 journal Oomens AG, Bevis KP, Wertz GW 2006 80 21 10465-10477 Journal of virology Pei et al., 2021 journal Pei J, Wagner ND, Zou AJ, Chatterjee S, Borek D, Cole AR, Kim PJ, Basler CF, Otwinowski Z, Gross ML, Amarasinghe GK, Leung DW 2021 118 10 Proceedings of the National Academy of Sciences of the United States of America Sadoff et al., 2021 journal Sadoff J, De Paepe E, Haazen W, Omoruyi E, Bastian AR, Comeaux C, Heijnen E, Strout C, Schuitemaker H, Callendret B 2021 223 4 699-708 The Journal of infectious diseases Schmidt et al., 2001 journal Schmidt AC, McAuliffe JM, Murphy BR, Collins PL 2001 75 10 4594-4603 Journal of virology Shahriari et al., 2018 journal Shahriari S, Wei KJ, Ghildyal R 2018 10 10 Viruses Simabuco et al., 2011 journal Simabuco FM, Asara JM, Guerrero MC, Libermann TA, Zerbini LF, Ventura AM 2011 42 1 340-345 Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] Tang et al., 2003 journal Tang RS, Schickli JH, MacPhail M, Fernandes F, Bicha L, Spaete J, Fouchier RA, Osterhaus AD, Spaete R, Haller AA 2003 77 20 10819-10828 Journal of virology Tiong-Yip et al., 2014 journal Tiong-Yip CL, Aschenbrenner L, Johnson KD, McLaughlin RE, Fan J, Challa S, Xiong H, Yu Q 2014 58 7 3867-3873 Antimicrobial agents and chemotherapy Tripp et al., 2018 journal Tripp RA, Power UF, Openshaw PJM, Kauvar LM 2018 92 3 Journal of virology Wiki: Human respiratory syncytial virus website http://microbewiki.kenyon.edu/index.php/Human_respiratory_syncytial_virus Wu et al., 2009 journal Wu H, Dennis VA, Pillai SR, Singh SR 2009 145 1 39-47 Virus research