Pan-SARS neutralizing responses after third boost vaccination in non-human primate immunogenicity model.

The emergence of SARS-CoV-2 variants, especially Beta and Delta, has raised concerns about the reduced protection from previous infection or vaccination based on the original Wuhan-Hu-1 (D614) virus. To identify promising regimens for inducing neutralizing titers towards new variants, we evaluated monovalent and bivalent mRNA vaccines either as primary vaccination or as a booster in nonhuman primates (NHPs). Two mRNA vaccines, D614-based MRT5500 and Beta-based MRT5500β, tested in sequential regimens or as a bivalent combination in naïve NHPs produced modest neutralizing titers to heterologous variants. However, when mRNA vaccines were administered as a booster to pre-immune NHPs, we observed a robust increase in neutralizing titers with expanded breadth towards all tested variants, and notably SARS-CoV-1. The breadth of the neutralizing response was independent of vaccine sequence or modality, as we further showed either MRT5500 or recombinant subunit Spike protein (with adjuvant) can serve as boosters to induce broadly neutralizing antibodies in the NHPs primed with MRT5500. The data support the notion that a third vaccination is key to boosting existing titers and improving the breadth of antibodies to address variants of concern, including those with an E484K mutation in the Receptor Binding Domain (RBD) (Beta, Gamma).

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Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kirill V. Kalnin, Michael Kishko, Dean Huang, Alice Raillard, Julie Piolat, Natalie G. Anosova, Tim Tibbitts, Joshua DiNapoli, Sudha Chivukula, Victoria Landolfi, Tong-Ming Fu, and Danilo Casimiro are current or former employees of Sanofi Pasteur and may hold stock in Sanofi company. Frank DeRosa, Shrirang Karve, Rebecca Goldman, Hardip Gopani, Anusha Dias, Khang Tran, Minnie Zacharia, Xiaobo Gu, Lianne Boeglin, Jonathan Abysalh, Jorel Vargas, Angela Beaulieu, Monic Shah, Travis Jeannotte, Kimberly Gillis, and Ron Swearingen are employees of Translate Bio and may hold stock in the company (TBio). Timothy Plitnik declares no competing interests. The research is funded by Translate Bio and Sanofi Pasteur.