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Introduction
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the development and approval of the Omicron-containing bivalent messenger ribonucleic acid (mRNA) COVID-19 vaccines1, and, approval of a Beta-variant containing recombinant protein-based booster vaccine with AS03 adjuvant (MVB.1.351) in Europe and the United Kingdom2. The efficacy of monovalent ancestral Spike-based vaccinations was substantial following their release in late 2020. Nonetheless, reductions in vaccination efficacy (VE) in the Omicron-dominant phase against infection and COVID-19-related hospitalization have been noted due to diminishing protection with time and discrepancies between the virus for which the original vaccines were formulated and the evolving circulating variations. The Omicron variation, which surfaced in November 2021, had heightened immune evasion relative to prior variants. A third monovalent booster dose conferred enhanced protection against infection and severe disease during the Omicron predominance; however, the vaccine efficacy of monovalent booster doses against COVID-19-associated hospitalization has diminished over time since administration, particularly during the recent periods dominated by the BA.2/BA.2.12.1 and BA.4/BA.5 sublineages. We previously reported safety and immunogenicity data measured at 15 days after booster from a head-to-head randomized trial comparing monovalent (MV) ancestral and MVB.1.351 adjuvanted vaccines (Sanofi) to the mRNA BNT162b2 MV ancestral strain vaccine (Pfizer-BioNTech)3. Our study showed that the MVB.1.351 induced higher neutralizing antibodies (NAbs) against a broad panel of variants (i.e., ancestral strain, Beta, Delta, Omicron BA.1) than homologous boosting with BNT162b2 vaccine.
Here, we report the persistence of cross-neutralizing antibodies, including against Omicron BA.4/5, extended up to 1 and 3 months after booster from the same study. Results from this study show that MVB.1.351 vaccination as a third dose following two-dose primary vaccination produces superior and long-lasting cross-neutralizing antibodies, up to 3 months after boosting as compared to an MV ancestral BNT162b2 mRNA vaccine or the MVD614 vaccine.
Methods
Study design
The design of this multicenter, randomized, single-blind trial (ClinicalTrials.gov NCT05124171; EudraCT number 2021004550-33) has been previously described3. Briefly, between December 8, 2021 (first participant first visit) and January 14, 2022 (last participant first visit), adult participants who had received primary vaccination with two doses of ancestral strain based BNT162b2 (second administration received between 3 and 7 months earlier) and who had given informed consent to take...