Declining Levels of Neutralizing Antibodies to SARS-CoV-2 Omicron Variants Are Enhanced by Hybrid Immunity and Original/Omicron Bivalent Vaccination

Author:

Walmsley Sharon12ORCID,Nabipoor Majid3ORCID,Qi Freda4,Lovblom Leif Erik3ORCID,Ravindran Rizani1,Colwill Karen4ORCID,Dayam Roya Monica4,Tursun Tulunay R.4,Silva Amanda5,Gingras Anne-Claude46ORCID,

Affiliation:

1. Division of Infectious Diseases, University Health Network, Toronto, ON M5G 2C4, Canada

2. Department of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada

3. Biostatistics Department, University Health Network, Toronto, ON M5G 2C4, Canada

4. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada

5. DATA Team, University Health Network, Toronto, ON M5G 2C4, Canada

6. Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada

Abstract

We determined neutralizing antibody levels to the ancestral Wuhan SARS-CoV-2 strain and three Omicron variants, namely BA.5, XBB.1.5, and EG.5, in a heavily vaccinated cohort of 178 adults 15–19 months after the initial vaccine series and prospectively after 4 months. Although all participants had detectable neutralizing antibodies to Wuhan, the proportion with detectable neutralizing antibodies to the Omicron variants was decreased, and the levels were lower. Individuals with hybrid immunity at the baseline visit and those receiving the Original/Omicron bivalent vaccine between the two sampling times demonstrated increased neutralizing antibodies to all strains. Both a higher baseline neutralizing antibody titer to Omicron BA.5 and hybrid immunity were associated with protection against a breakthrough SARS-CoV-2 infection during a 4-month period of follow up during the Omicron BA.5 wave. Neither were associated with protection from a breakthrough infection at 10 months follow up. Receipt of an Original/Omicron BA.4/5 vaccine was associated with protection from a breakthrough infection at both 4 and 10 months follow up. This work demonstrates neutralizing antibody escape with the emerging Omicron variants and supports the use of additional vaccine doses with components that match circulating SARS-CoV-2 variants. A threshold value for neutralizing antibodies for protection against reinfection cannot be determined.

Funder

Public Health Agency of Canada

University Health Network Foundation

Publisher

MDPI AG

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