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. 2025 Jan 18;5(1):21.
doi: 10.1038/s43856-024-00675-9.

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

Odile Launay  1 , Rachna Gupta  2 , Tifany Machabert  3 , Eleine Konate  4 , Alexandra Rousseau  5 , Claire Vigne  6 , Francois Beckers  3 , Louis Devlin  2 , Elisabeth Botelho-Nevers  7 , Marine Cachanado  5 , Christian Chidiac  8 , Dominique Deplanque  9 , Bertrand Dussol  10 , Inès Ben Ghezala  11 , Marie Lachatre  4 , Karine Lacombe  12 , Fabrice Laine  13 , Liem Binh Luong Nguyen  4 , Patricia Pavese  14 , Catherine Schmidt-Mutter  15 , Marie-Pierre Tavolacci  16 , Roman M Chicz  17 , Bogdana Coudsy  6 , Saranya Sridhar  18 , Amel Touati  5 , Eric Tartour  19 , Tabassome Simon  20
Affiliations

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

Odile Launay et al. Commun Med (Lond). .

Abstract

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 summary

The 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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Conflict of interest statement

Competing interests: The authors declare the following competing interests: R.G., T.M., C.V., F.B., L.D., R.M.C., B.C. and S.S. are Sanofi employees and may hold stocks/shares in the company. O.L. reports grant from French Ministry of Health and grants or contracts from Pfizer, Sanofi-Pasteur, GSK, MSD, MD, AstraZeneca, and Johnson & Johnson. T.S. reports grant from AstraZeneca, Novartis, Sanofi, Bayer and personal fees for board membership and consulting. K.L. reports personal fees and fees for development of educational presentations from Gilead, MSD, Janssen, ViiV, Spikimm, Janssen, Sobi, and Chiesi. EBN has received grant pending from Sanofi Pasteur and fees for board membership from Pfizer, and Janssen. L.B.L.N. received personal fees for advisory experts and participation to conference from Pfizer. All other authors have no competing interests to declare.

Figures

Fig. 1
Fig. 1. Summary of participant disposition in the study and per protocol analysis sets.
N: number of participants in the Revised Per-Protocol Analysis Set Monogram; MV: Monovalent, PPAS: per protocol population, MNA: microneutralization assay. The Revised Per-Protocol Analysis Set Monogram was used for statistical analysis and comprised all randomized participants who received the booster, did not have prespecified major protocol deviations, those who reconsented for sending their samples for pseudovirus neutralization antibody testing, who were not screen failures and excluded participants with a positive anti-nucleocapsid serology at D0, D14, or D28 or lost to follow-up. Evaluation of the subset of selected participants based on availability of samples for this re-analysis indicated comparability in baseline characteristics of sex and age (assessed both categorically and continuously) and no systematic bias in the definition or composition of these participants.
Fig. 2
Fig. 2. Kinetics of post-booster neutralization antibody responses against Omicron BA.1 and BA.4/5 variant strains assessed prior to, at 28 days and 3 months after receipt of a third vaccine dose (Revised Per-Protocol analysis set Monogram).
Shown are geometric mean titers of neutralizing antibodies against the Omicron BA.1 (A–C) and BA.4/5 (D–F) variant strains of SARS- CoV-2. The blue line, red even dashes, and green uneven dashes indicate BNT162b2, Sanofi B.1.351, and Sanofi D614 vaccines, respectively. Circles represent the GMT values at 0, 28 days and 3 months after receipt of a third vaccine dose. Error bars indicate 95% confidence intervals for the GMTs. A and D depict all participants, B and E show GMTs for subgroup of participants without SARS-CoV-2 infection up to 3 months post-booster, and C and F show GMTs for subgroup of participants with SARS-CoV-2 infection identified between D28 and M3. Please refer to Table 4 for the number of participants at each time point. Infected participants were defined with either a positive anti-nucleocapsid serology at M3 or who developed clinical symptoms with confirmatory testing for SARS CoV-2 between D28 and M3. SARS-CoV-2 neutralizing antibody responses were measured using a lentivirus-based pseudovirus neutralization (PsVN) assay expressing the full-length S protein of the SARS-CoV-2 D614G or Omicron (BA.1 or BA.4/5) variants. Laboratory testing was performed by staff who were blinded to group allocation and time points. The figure was created using SAS® 9.4.
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