Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection

Author:

Evans John P.123ORCID,Zeng Cong12ORCID,Carlin Claire4ORCID,Lozanski Gerard5ORCID,Saif Linda J.678ORCID,Oltz Eugene M.9ORCID,Gumina Richard J.4ORCID,Liu Shan-Lu1289ORCID

Affiliation:

1. Center for Retrovirus Research, Ohio State University, Columbus, OH 43210, USA.

2. Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210, USA.

3. Molecular, Cellular, and Developmental Biology Program, Ohio State University, Columbus, OH 43210, USA.

4. Division of Cardiovascular Medicine, Department of Internal Medicine, Ohio State University, Columbus, OH 43210, USA.

5. Department of Pathology, Ohio State University, Columbus, OH 43210, USA.

6. Center for Food Animal Health, Animal Sciences Department, OARDC, College of Food, Agricultural and Environmental Sciences, Ohio State University, Wooster, OH 44691, USA.

7. Veterinary Preventive Medicine Department, College of Veterinary Medicine, Ohio State University, Wooster, OH 44691, USA.

8. Viruses and Emerging Pathogens Program, Infectious Diseases Institute, Ohio State University, Columbus, OH 43210, USA.

9. Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH 43210, USA.

Abstract

The waning efficacy of SARS-CoV-2 vaccines, combined with the continued emergence of variants resistant to vaccine-induced immunity, has reignited debate over the need for booster vaccine doses. To address this, we examined the neutralizing antibody response against the spike protein of five major SARS-CoV-2 variants, D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), in health care workers (HCWs) vaccinated with SARS-CoV-2 mRNA vaccines. Serum samples were collected before vaccination, 3 weeks after first vaccination, 1 month after second vaccination, and 6 months after second vaccination. Minimal neutralizing antibody titers were detected against Omicron pseudovirus at all four time points, including for most patients who had SARS-CoV-2 breakthrough infections. Neutralizing antibody titers against all other variant spike protein–bearing pseudoviruses declined markedly from 1 to 6 months after the second mRNA vaccine dose, although SARS-CoV-2 infection boosted vaccine responses. In addition, mRNA-1273–vaccinated HCWs exhibited about twofold higher neutralizing antibody titers than BNT162b2-vaccinated HCWs. Together, these results demonstrate possible waning of antibody-mediated protection against SARS-CoV-2 variants that is dependent on prior infection status and the mRNA vaccine received. They also show that the Omicron variant spike protein can almost completely escape from neutralizing antibodies elicited in recipients of only two mRNA vaccine doses.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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