Efficacy of mRNA-1273 and Novavax ancestral or BA.1 spike booster vaccines against SARS-CoV-2 BA.5 infection in non-human primates

• Type of Material: Article
• Authors: Nanda Kishore Routhu, Emory University; Samuel Stampfer, Emory University; Lilin Lai, Emory University; Akil Akhtar, Emory University; Xin Tong, Massachusetts Institute of Technology; Dansu Yuan, Massachusetts Institute of Technology; Taras M. Chicz, Massachusetts Institute of Technology; Ryan P. McNamara, Massachusetts Institute of Technology; Kishor Jakkala, Emory University; Meredith E. Davis-Gardner, Emory University; E. Lovisa St Pierre, Tulane National Primate Research Center; Brandon Smith, Tulane National Primate Research Center; Kristyn Moore Green, Tulane National Primate Research Center; Nadia Golden, Tulane National Primate Research Center; Breanna Picou, Tulane National Primate Research Center; Sherrie Jean, Emory University; Jennifer S Wood, Emory University; Joyce Cohen, Emory University; Ian N. Moore, Emory University; Nita Patel, Novavax, Inc.; Mimi Guebre-Xabier, Novavax, Inc.; Gale Smith, Novavax, Inc.; Greg Glenn, Novavax, Inc.; Pamela A. Kozlowski, Louisiana State University; Galit Alter, Massachusetts Institute of Technology; Rafi Ahmed, Emory University; Mehul Suthar, Emory University; Rama Rao Amara, Emory University
• Language: English
• Date: 2023-05-16
• Publisher: American Association for the Advancement of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1126%2Fsciimmunol.adg7015
• Title of Journal or Parent Work: Science Immunology
• Volume: 16
• Start Page: eadg7015
• Grant/Funding Information: This work was supported in part by NIH Grants RO1 AI148378-01S1 and Fast Grants awards #2166 and #2209 to R.R.A., the NIH/NIAID CEIRR contract 75N93021C00017 to Emory University, the ORIP/NIH base grant P51 OD011132 to ENPRC, and NIH grants AI26683 and OD010976 to Nonhuman Primate Reagent Resource. S.D.S received support from the NIH/NIAID award T32AI074492.; Rhesus dimeric IgA (b12rA1d) was obtained from the NIH Nonhuman Primate Reagent Resource supported by AI26683 and OD010976.
• Keywords: mRNA-1273; BA.1 spike booster vaccines; SARS-CoV-2
• Research Categories: Biology, Virology

Abstract

Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.1 spike protein version (NVX-CoV2515). All three booster vaccines induced a strong BA.1 cross-reactive binding antibody and changed immunoglobulin G dominance from IgG1 to IgG4 in the serum. All three booster vaccines also induced strong and comparable neutralizing antibody responses against multiple variants of concern, including BA.5 and BQ.1.1, along with long-lived plasma cells in the bone marrow. The ratio of BA.1 to WA-1 spike-specific antibody-secreting cells in the blood was higher in NVX-CoV2515 animals compared to NVX-CoV2373 animals, suggesting a better recall of BA.1 specific memory B cells by the BA.1 spike-specific vaccine compared to the ancestral spike-specific vaccine. Further, all three booster vaccines induced low levels of spike-specific CD4 but not CD8 T cell responses in the blood. Following challenge with SARS-CoV-2 BA.5 variant, all three vaccines showed strong protection in the lungs and controlled virus replication in the nasopharynx. In addition, both Novavax vaccines blunted viral replication in nasopharynx at day 2. The protection against SARS-CoV-2 BA.5 infection in the upper respiratory airways correlated with binding, neutralizing, and ADNP activities of the serum antibody. These data have important implications for COVID-19 vaccine development, as vaccines that lower nasopharyngeal virus may help to reduce transmission.