Side-by-side comparison of SARS-CoV-2 neutralizing antibody responses after various COVID-19 vaccine regimens

Title

Side-by-side comparison of SARS-CoV-2 neutralizing antibody responses after various COVID-19 vaccine regimens

Presenter

Delphine Planas

Authors

D. Planas * (1), I. Staropoli (1), F. Guivel-Benhassine (1), F. Porrot (1), D. Veyer (2), H. Péré (2), C. Planchais (1), A.P. Pessoa Vilela (3), S. Maia Acuña (3), M. dos Passos Cunha (3), J. Hadjad (4), B. Terrier (4), A. Seve (5), H. Mouquet (1), P. Minoprio (3), T. Prazuck (5), L. Hocqueloux (5), T. Bruel (1), O. Schwartz (1)

Institutions

(1) Institut Pasteur, Virology, Paris, France, (2) Hôpital Européen Georges Pompidou, Laboratoire de Virologie, Service de Microbiologie, Paris, France, (3) Institut Pasteur, São Paulo, Brazil, (4) Hôpital Cochin, Department of Internal Medicine, Paris, France, (5) CHR d'Orléans, Infectious Diseases, Orléans, France

BACKGROUND: Waning immunity and emergence of SARS-CoV-2 variants impact COVID-19 vaccine efficacy. Here, we studied longitudinally the humoral response induced by Pfizer, AstraZeneca, Janssen, Coronavac and Sputnik Vaccines, with or without booster doses. We also asked how breakthrough Omicron infection in Pfizer-vaccinated individuals enhances antibody levels and cross-reactivity.
METHODS: We analyzed 349 sera from individuals immunized with five vaccines, Pfizer/BioNTech (BNT162b2), AstraZeneca (ChAdOx1 nCoV-19), Janssen (Ad26COV2.S), Sinovac biotech (Coronavac) or Sputnik (Gam-COVID-Vac). We also examined in 92 sera the impact of a Pfizer booster dose in individuals immunized with Pfizer, Janssen or Sinovac regimens. Samples were collected up to 13 months after the first injection, and 5 months after the boost. We measured anti-S antibodies by flow cytometry with the S-Flow assay, and neutralization titers against infectious D614G, Alpha, Beta, Delta and Omicron isolates.
RESULTS: Administration of two doses of Pfizer, AstraZeneca, Sputnik vaccines, or an heterologous AstraZeneca/Pfizer regimen, induced seroconversion of 95% of individuals and neutralization activity against D614G, Alpha, Beta and Delta, but not Omicron. Janssen and Sinovac vaccines elicited lower levels of anti-S antibodies, and no detectable neutralization of Delta and Omicron. During the first 8 months, the antibody levels and neutralization activity progressively declined with all vaccines. A booster dose of Pfizer strongly increased antibody response and elicited neutralizing antibodies against Omicron. However, titers were 8- to 36- fold lower against Omicron relative to Delta. We observed a waning of the humoral response after the boost and estimated that neutralizing antibodies against Omicron will no longer be detectable in the sera after 6 months. Breakthrough Omicron infections strongly increased the levels of cross-reactive antibodies with titers only 2.5-fold lower against Omicron compared to Delta.
CONCLUSIONS: Our results highlight differences between vaccines and support the use of an mRNA-based vaccine as a booster regardless of prior regimens. The duration of the neutralizing humoral response after the boost is estimated to be about 6 months. A high level of cross-reactivity is observed in Omicron breakthrough cases. Our data suggest that an Omicron-specific booster may improve cross-immunity.

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