Beta-variant recombinant SARS CoV-2 vaccine induces durable cross-reactive antibodies against Omicron BA variants

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Launay, Odile | Gupta, Rachna | Machabert, Tifany | Konaté, Eleine | Rousseau, Alexandra | Vigne, Claire | Beckers, Francois | Devlin, Louis | Botelho-Nevers, Elisabeth | Cachanado, Marine | Chidiac, Christian | Deplanque, Dominique | Dussol, Bertrand | Ben Ghezala, Ines | Lachâtre, Marie | Lacombe, Karine | Lainé, Fabrice | Binh Luong Nguyen, Liem | Pavese, Patricia | Schmidt-Mutter, Catherine | Tavolacci, Marie-Pierre | Chicz, Roman, M | Coudsy, Bogdana | Sridhar, Saranya | Touati, Amel | Tartour, Eric | Simon, Tabassome

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International audience. Background: We previously reported the safety and immunogenicity data from a randomized trial comparing the booster responses of vaccinees who received monovalent (MV) recombinant protein Beta-variant (MVB.1.351) and MV ancestral protein (MVD614) vaccines with AS03 adjuvant (Sanofi/GSK) to booster response of vaccinees who received mRNA MV ancestral strain BNT162b2 vaccine (Pfizer-BioNTech).Methods: First booster of the vaccines was administered in adult participants previously primed with 2 doses of MV ancestral strain BNT162b2. A subset of these participants with available blood samples collected at Day 0 (D0), at 28 days (D28), and 3 months (M3) post-booster were contacted for additional testing (195/208 participants). The persistence of cross-neutralizing antibodies, including against Omicron BA.1 and BA.4/5, up to 3 months after boosting was evaluated using a validated pseudovirus neutralization assay.Results: Across the whole population, MVB.1.351 vaccine induces highest NAbs titers against Omicron BA.1 and BA.4/5 variants at D28 and M3 post-booster. In participants with SARS-CoV-2 infection between D28 and M3, both MVB.1.351 and BNT162b2 vaccine groups show an increase in GMTs against Omicron BA.1 and Omicron BA.4/5 following infection. Among uninfected participants, the ratio of M3 to D28 GMTs was higher for the MVB.1.351 group than the BNT162b2 group against Omicron BA.1 (0.64 [0.53;0.77] versus 0.43 [0.35;0.53]), Omicron BA.4/5 (0.61 [0.50; 0.75] versus 0.44 [0.34; 0.56]), and D614 (0.68 [0.58,0.81] versus 0.46 [0.39,0.55]).Conclusions: The MVB.1.351 vaccine induces higher and durable cross-neutralizing antibodies against Omicron subvariants up to 3 months after boosting compared to an MV ancestral and mRNA BNT162b2 booster vaccine.Plain language summaryThe SARS-CoV-2 virus has changed over time, resulting in new virus variants. It is important to understand how booster vaccines work against different virus variants and how long protection may last. We compared the impact of different COVID-19 vaccines on the immune response of people who had previously received an original licensed mRNA vaccine and then received a third dose (first booster) with either the same type of mRNA-based vaccine or with one of two protein-based vaccines. None of these vaccines contained the omicron variant. We saw differences in response depending on the different combinations of vaccine used. Our results suggest booster vaccination using different types of vaccines could enable people to have better protection against SARS-CoV-2 infection. This should be considered when considering which COVID-19 vaccines to use during booster vaccination programs.

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