A Phase 3, randomized, non-inferiority study of a heterologous booster dose of SARS CoV-2 recombinant spike protein vaccine in adults
Authors: Kulkarni Prasad S. , Gunale Bhagwat , Kohli Sunil , Lalwani Sanjay , Tripathy Srikanth , Kar Sonali , Raut Sidram , Kulkarni Praveen , Apte Aditi , Bavdekar Ashish , Bhalla Hira Lal , Plested Joyce S. , Cloney-Clark Shane , Zhu MingZhu , Kalkeri Raj , Pryor Melinda , Hamilton Stephanie , Thakar Madhuri , Sannidhi Ranga S. , Baranwal Punjita , Bhamare Chetanraj , Dharmadhikari Abhijeet , Gupta Manish , Poonawalla Cyrus S. , Shaligram Umesh , Kapse Dhananjay ,   COVOVAX-Booster Study Group, Jain Vineet , Goyal Nidhi , Arya Alok , Rongsen-Chandola Temsunaro , Palkar Sonali , Hanumante Neeta , Kakrani Arjun , Mirza Shahzad Beg , Mahajan Savita , Kothavale Rakesh , Samantaray Pramod Chandra , Kodre Aparna , Mythily M. R. , Shwethashree M. , Dayma Girish , Patel Tejas , Kishore Surekha 
Published: October 2023

Due to waning immunity following primary immunization with COVID-19 vaccines, booster doses may be required. The present study assessed a heterologous booster of SII-NVX-CoV2373 (spike protein vaccine) in adults primed with viral vector and inactivated vaccines. In this Phase 3, observer-blind, randomized, active controlled study, a total of 372 adults primed with two doses of ChAdOx1 nCoV-19 (n = 186) or BBV152 (n = 186) at least six months ago, were randomized to receive a booster of SII-NVX-CoV2373 or control vaccine (homologous booster of ChAdOx1 nCoV-19 or BBV152). Anti-S IgG and neutralizing antibodies (nAbs) were assessed at days 1, 29, and 181. Non-inferiority (NI) of SII-NVX-CoV2373 to the control vaccine was assessed based on the ratio of geometric mean ELISA units (GMEU) of anti-S IgG and geometric mean titers (GMT) of nAbs (NI margin > 0.67) as well as seroresponse (≥ 2 fold-rise in titers) (NI margin −10%) at day 29. Safety was assessed throughout the study period. In both the ChAdOx1 nCoV-19 prime and BBV152 prime cohorts, 186 participants each received the study vaccines. In the ChAdOx1 nCoV-19 prime cohort, the GMEU ratio was 2.05 (95% CI 1.73, 2.43) and the GMT ratio was 1.89 (95% CI 1.55, 2.32) whereas the difference in the proportion of seroresponse was 49.32% (95% CI 36.49, 60.45) for anti-S IgG and 15% (95% CI 5.65, 25.05) for nAbs on day 29. In the BBV152 prime cohort, the GMEU ratio was 5.12 (95% CI 4.20, 6.24) and the GMT ratio was 4.80 (95% CI 3.76, 6.12) whereas the difference in the proportion of seroresponse was 74.08% (95% CI 63.24, 82.17) for anti-S IgG and 24.71% (95% CI 16.26, 34.62) for nAbs on day 29. The non-inferiority of SII-NVX-CoV2373 booster to the control vaccine for each prime cohort was met. SII-NVX-CoV2373 booster showed significantly higher immune responses than BBV152 homologous booster. On day 181, seroresponse rates were ≥ 70% in all the groups for both nAbs and anti-S IgG. Solicited adverse events reported were transient and mostly mild in severity in all the groups. No causally related SAE was reported. SII-NVX-CoV2373 as a heterologous booster induced non-inferior immune responses as compared to homologous boosters in adults primed with ChAdOx1 nCoV-19 and BBV152. SII-NVX-CoV2373 showed a numerically higher boosting effect than homologous boosters. The vaccine was also safe and well tolerated.