The bivalent mRNA vaccine booster Omicron BA.4/BA.5 elicits similar neutralizing antibody responses as the monovalent vaccine

In a study recently published on the bioRxiv* Preprint servers, researchers analyzed the antibody response induced by the new bivalent messenger ribonucleic acid (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects fully vaccinated with monovalent vaccines , and those that had a breakthrough infection with the SARS-CoV-2 Omicron BA.4/BA.5 variants.

background

The evolution of the SARS-CoV-2 virus has led to the emergence of many more infectious variants than the ancestral strain. The SARS-CoV-2 omicron variant and many of its sublineages have been shown to remarkably escape humoral immunity acquired through previous infection or vaccination.

Recently, the United States Food and Drug Administration (FDA) issued emergency use authorizations (EUAs) for new bivalent messenger ribonucleic acid (mRNA) vaccine formulations of the original Pfizer and Moderna vaccines. These bivalent mRNA vaccines target the spike protein of both the SARS-CoV-2 ancestral strain and the SARS-CoV-2 variant Omicron BA.4/BA.5.

Published data on neutralizing antibody responses induced by bivalent mRNA vaccines are limited to animal and human studies with a bivalent vaccine targeting the Omicron BA.1 spike protein and the wild-type strain. Despite the extensive use of the new bivalent mRNA vaccines Omicron BA.4/BA.5 as booster doses, very little information is available on the antibody responses they elicit in humans.

About the study

In the present study, researchers collected sera from multiple cohorts, including 1) subjects who received three or four doses of monovalent mRNA vaccine, 2) subjects who developed breakthrough infection with the Omicron BA.4/BA.5 variant after monovalent mRNA had vaccination and 3) those receiving the bivalent mRNA vaccines as a fourth dose.

The team used pseudovirus neutralization assays to test the sera for neutralization against the SARS-CoV-2 ancestral virus, Omicron sublines and other related sarbecoviruses. They compared virus neutralization by sera from subjects vaccinated with three doses of the original monovalent vaccine and a fourth dose of the bivalent BA.4/BA.5 vaccine with sera from subjects vaccinated with three or four monovalent vaccines and subjects with Omicron BA were vaccinated .4/BA.5 breakthrough infection after mRNA vaccination.

They tested all collected sera for neutralization against the SARS-CoV-2 virus strain D614G and the omicrons BA.1/BA.2, BA.4/BA.5, BA.4.6, BA.2.75 and BA.2.75. 2 sub lines. They also tested the sera against many related sarbecoviruses, including GD-pangolin, SARS-CoV and WIV1.

Subjects vaccinated with four monovalent vaccine doses were older, with a mean age of 55.3 years, than those receiving a bivalent booster, with a mean age of 36.4 years. Sera were collected from all cohorts at similar time points after booster vaccination (mean 24.0 days for the monovalent group and mean 26.4 days for the bivalent cohort).

Results

All groups had the highest neutralizing antibody titers (ID50) against SARS-CoV-2 strain D614G. Boosted sera had the lowest geometric mean ID50 titers and BA.4/BA.5 breakthrough sera had the highest ID50 titers against SARS-CoV-2 variants. No significant difference in neutralization was observed between subjects who received four monovalent vaccine doses and subjects who received a bivalent vaccine as the fourth dose for any of the tested SARS-CoV-2 variants.

Interestingly, in the case of the three related sarbecoviruses – WIV1, SARS-CoV and GD-pangolin – the neutralizing antibody titers of individuals who received a fourth dose of monovalent vaccine were slightly but significantly higher than those who received the bivalent vaccine as A fourth vaccine dose.

The researchers observed that people who received the bivalent mRNA vaccine as a fourth dose had neutralizing antibody titers about three to five weeks after the booster dose that were similar to those who received a monovalent mRNA vaccine as a fourth dose against all SARS-CoV-2 received variants tested in the study, including the Omicron BA.4/BA.5 sublines.

Conclusion

Overall, at the time of the study, a bivalent mRNA vaccine administered as the fourth dose and directed against the SARS-CoV-2 ancestral strain and Omicron BA.4/BA.5 did not induce stronger neutralizing antibody responses compared to the monovalents vaccines. According to the authors, the above findings could indicate an immunological imprint. Further follow-up would help determine if neutralizing antibody responses to the bivalent vaccine decrease over time, including antibody responses to a second bivalent booster vaccine.

*Important NOTE

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health behavior, or be treated as established information.