Bivalent mRNA booster broadens humoral immunity against SARS-CoV-2 Omicron subvariants

In a recent study posted to the bioRxiv* server, researchers at Emory University, Stanford University, and the National Institute of Allergy and Infectious Diseases evaluated whether bivalent coronavirus disease 2019 (COVID-19) boosters conferred protection against new Omicron subvariants.

Study: mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1. Image Credit: NIAID

Background

Two new subvariants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron, BA.2.75.2 and BQ.1.1, share the R346T mutation. It is of particular concern because it substantially reduces the efficacy of bivalent COVID-19 messenger ribonucleic acid (mRNA) boosters. These novel booster vaccines have been introduced recently in the US post the emergence of highly mutated Omicron VOC. They use the ancestral and the Omicron BA.5 spike (S) as immunogens.

However, after their authorization and uptake, more Omicron subvariants have been identified with mutations in the receptor binding domain (RBD) that confer them with the potential to escape vaccine sera. In fact, the R346T mutation, which has arisen in many Omicron subvariants, confers them with the potential to escape vaccine-elicited and approved monoclonal antibodies.

About the study

The present study evaluated serum samples from vaccine booster recipients divided into three cohorts. The first, second, and third study cohorts comprised one monovalent booster, two monovalent boosters, and bivalent booster recipients. The team collected serum samples from seven to 28 days, 70 to 100 days, and 16 to 42 days after booster vaccinations from these three cohorts.

They used an in vitro live-virus focus neutralization test (FRNT) assay for quantifying neutralizing antibody response among these three cohorts. More specifically, they compared FRNT₅₀ geometric mean titers (GMT) of Omicron subvariants, including BA.1, BA.5, BA.2.75.2, and BQ.1.1. against the wild-type SARS-CoV-2 strain. For samples with a low limit of detection (LoD) of 1:20, the researchers assigned an arbitrary FRNT₅₀ of 10.

Study findings and conclusion

Individuals in the study cohorts that received one or two monovalent boosters exhibited much-reduced FRNT titers against Omicron subvariants. The effect was most profound against BA.2.75.2 and BQ.1.1, which have the R346T mutation. On the contrary, BA.5-containing bivalent booster recipients exhibited good neutralizing activity against all Omicron subvariants.

In the monovalent booster cohort, the FRNT₅₀ GMTs for WT strain, BA.1, BA.5, BA.2.75.2, and BQ.1.1. were 758, 60, 50, 23, and 19, respectively. For the two monovalent booster cohorts, the FRNT₅₀ GMTs were 1812, 205, 142, 65, and 53 for WT strain, BA.1, BA.5, BA.2.75.2, and BQ.1.1, respectively. Compared to WT, the overall reduction in neutralization titers varied for different Omicron subvariants. It decreased from nine to 15 and 28 to 39-fold for BA.1 and BA.5, and BA.2.75.2 and BQ.1.1., respectively.

Likewise, relative to the WT strain, the authors observed a reduction in neutralization titers of four-fold against BA.1 and BA.5 and 11- and 21-fold against BA.2.75.2 and BQ.1.1, respectively, in the bivalent booster cohort. The BA.5-containing bivalent booster recipients neutralized all Omicron subvariants more effectively. This observation was consistent with findings in individuals with breakthrough Omicron infections. They also showed broadened neutralizing activity against other Omicron subvariants.

The study results suggested that the bivalent mRNA booster vaccine broadened humoral immunity against the Omicron subvariants. Indeed, there is a substantial serological benefit of bivalent booster immunizations.

*Important notice

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

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.