Early results from randomized trial of @BharatBiotech nasal vaccine (BBV154, approved in India) vs injections now published, superior antibodies and cellular immune response (vs ancestral and Omicron); 4 times fewer side effects
Although the number of COVID-19 cases and deaths is substantially lower globally than at the peak of the pandemic, the continued emergence of SARS-CoV-2 variants of concern (VOCs), including the most recent highly transmissible Omicron variants They mean the threat of the pandemic is not over. Therefore, efforts to provide protection through prophylactic vaccination must continue. However, all currently authorized injectable SARS-CoV-2 vaccines have decreased efficacy against emerging VOCs whose mutated forms of the S protein make them less susceptible to the vaccine. Additionally, there is limited vaccine efficacy against asymptomatic infection and transmission of emerging variants.
The nasal mucosa is the first anatomical and immunological barrier that the SARS-CoV-2 virus must overcome to induce infection, so it may be critical to block SARS-CoV-2 infection and transmission that allows progressive infections in completely vaccinated. By producing both mucosal protective immunity at the site of infection and systemic immunity, an intranasal vaccine can be effective against disease and infection while also decreasing transmission.
Background:
Unlike intramuscular vaccines, intranasal COVID-19 vaccines can generate mucosal immunity, which may be critical in preventing infection and human-to-human transmission. We report the interim immunogenicity and safety of an intranasal adenoviral vector SARS-CoV-2 vaccine (BBV154, iNCOVACC®) in healthy adults compared to the licensed intramuscular vaccine (Covaxin®).
Methods:
In this open-label, multicenter, phase 3 clinical trial, healthy Indian adults were randomized to receive two doses of BBV154 (n = 3000) or Covaxin® (n = 160) 28 days apart.
The primary immunogenicity outcome was the geometric mean neutralizing antibody titers (PRNT50) against SARS-CoV-2 viruses; Key secondary outcomes were safety and reported adverse events, serum and secretory IgA responses, and cell-mediated immune responses.
Findings:
We screened 3,209 volunteers between April 16 and June 4, 2022 and enrolled and randomized 3,160 to receive BBV154 (n = 2,998) or Covaxin (n = 162). On day 42, 14 days after the second dose, serum GMTs against ancestral SARS-CoV-2 (Wuhan) were 769 (95% CI: 665‒888) and 531 (426‒662) in the BBV154 and Covaxin.
The GMT ratio of 1.45 (95% CI: 1.11‒1.88) met the predefined superiority criterion for BBV154 over Covaxin. BBV154 also caused higher serum neutralizing GMT [171 (137–213)] against Omicron BA.5 than Covaxin [82·4 (48·9–139)].
Similarly, at day 42, secretory IgA GMTs were 12.3 (95% CI 8.7-17.4) and 6.6 (95% CI 4.6-9.5) after from BBV154 and Covaxin; BBV154 was superior to Covaxin with a GMT ratio of 1.9 (95% CI: 1.1–3.0). BBV154 induced higher serum IgA titers and significantly higher levels of antibody-secreting plasmablasts at day 42.
Both vaccines induced equivalent T cell memory responses. Both vaccines were well tolerated , with systemic adverse events reported in 2.7% (82/2990) of BBV154 recipients and 6.2% (10/161) of Covaxin recipients. 4.9% (146/2990) of BBV154 participants experienced nasal reactions, while 23.0% (37/161) of those vaccinated with Covaxin® experienced local reactions at the injection site.
Conclusions
In conclusion , we have shown that intranasal application of two doses of BBV154 was generally well tolerated by adults, without the pain associated with intramuscular injections of Covaxin (control vaccine) and a lower rate of systemic adverse events, while it elicited a response superior humoral neutralizing against the ancestral strain of the SARS-CoV-2 virus, and cross-neutralizing activity against an Omicron variant. Additional clinical development of BBV154 is ongoing, including as part of a heterologous booster regimen in Phase 3 clinical trials.
Interpretation: Two intranasal doses of BBV154 were well tolerated without safety concerns and elicited superior humoral and mucosal immune responses compared to two intramuscular injections of Covaxin. Further studies are warranted to evaluate the effect of BBV154 on infection and transmission. |
Trial registration : The trial was registered with the Clinical Trials Registry of India, CTRI/2022/02/40065, and ClinicalTrials.gov, NCT05522335.
