1. Binding and Avidity Signatures of Polyclonal Sera From Individuals With Different Exposure Histories to Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Vaccination, and Omicron Breakthrough Infections.
- Author
-
Singh G, Abbad A, Tcheou J, Mendu DR, Firpo-Betancourt A, Gleason C, Srivastava K, Cordon-Cardo C, Simon V, Krammer F, and Carreño JM
- Subjects
- Animals, Humans, Chlorocebus aethiops, COVID-19 Serological Testing, Vaccination, Vero Cells, BNT162 Vaccine immunology, BNT162 Vaccine therapeutic use, Antibodies, Viral blood, Antibodies, Viral immunology, Antibody Affinity, Breakthrough Infections blood, Breakthrough Infections immunology, COVID-19 blood, COVID-19 immunology, COVID-19 prevention & control, SARS-CoV-2 immunology
- Abstract
Background: The number of exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to vaccine antigens affect the magnitude and avidity of the polyclonal response., Methods: We studied binding and avidity of different antibody isotypes to the spike, the receptor-binding domain (RBD), and the nucleoprotein (NP) of wild-type (WT) and BA.1 SARS-CoV-2 in convalescent, mRNA vaccinated and/or boosted, hybrid immune individuals and in individuals with breakthrough cases during the peak of the BA.1 wave., Results: We found an increase in spike-binding antibodies and antibody avidity with increasing number of exposures to infection and/or vaccination. NP antibodies were detectible in convalescent individuals and a proportion of breakthrough cases, but they displayed low avidity. Omicron breakthrough infections elicited high levels of cross-reactive antibodies between WT and BA.1 antigens in vaccinated individuals without prior infection directed against the spike and RBD. The magnitude of the antibody response and avidity correlated with neutralizing activity against WT virus., Conclusions: The magnitude and quality of the antibody response increased with the number of antigenic exposures, including breakthrough infections. However, cross-reactivity of the antibody response after BA.1 breakthroughs, was affected by the number of prior exposures., Competing Interests: Potential conflicts of interest. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays and Newcastle disease virus-based SARS-CoV-2 vaccines, which list F. K. as coinventor. A. F. B., C. C. C., and V. S. are also listed on the SARS-CoV-2 serological assays patent. Mount Sinai has spun out a company, Kantaro Biosciences, to market serological tests for SARS-CoV-2. F. K. has consulted for Merck and Pfizer (before 2020); is currently consulting for Pfizer, Seqirus, Third Rock Ventures, and Avimex; and is a cofounder and scientific advisory board member of CastleVax. The Krammer Laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2023
- Full Text
- View/download PDF