• Vaccine Name: COVAXIN
• Target Pathogen: SARS-CoV-2
• Target Disease: COVID-19
• Product Name: BBV152
• Manufacturer: Bharat Biotech
• Vaccine Ontology ID: VO_0004991
• Type: Inactivated or "killed" vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Adjuvant:
  • Adjuvant name:
  • VO adjuvant ID: VO_0005301
• Preparation: 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)
• Immunization Route: Intramuscular injection (i.m.)

Macaque Response

• Vaccination Protocol: 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.
• Immune Response: 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.
• Side Effects: Adverse events were not seen in animals immunized with a two-dose vaccination regimen.
• Challenge Protocol: 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.
• Efficacy: 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.

Human Response

• Vaccination Protocol: 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]
• Immune Response: 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]
• Efficacy: 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]