Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants

• Published in: Nature communications Vol. 14; no. 1; pp. 1130 - 16
• Main Authors: Logue, James, Johnson, Robert M., Patel, Nita, Zhou, Bin, Maciejewski, Sonia, Foreman, Bryant, Zhou, Haixia, Portnoff, Alyse D., Tian, Jing-Hui, Rehman, Asma, McGrath, Marisa E., Haupt, Robert E., Weston, Stuart M., Baracco, Lauren, Hammond, Holly, Guebre-Xabier, Mimi, Dillen, Carly, Madhangi, M., Greene, Ann M., Massare, Michael J., Glenn, Greg M., Smith, Gale, Frieman, Matthew B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.02.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 13; 13/1; 45/77; 631/326/590; 631/326/596; 631/326/596/4130; ACE2; Angiotensin-converting enzyme 2; Animals; Antibodies; Antibodies, Neutralizing; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines - chemistry; COVID-19 Vaccines - immunology; Health risks; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunization; Immunogenicity; Immunological memory; Lymphocytes T; Mice; multidisciplinary; Nanoparticles; Neutralization; Neutralizing; Papio; Primates; Proteins; SARS-CoV-2 - genetics; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike protein; Vaccines; Vaccines - chemistry; Vaccines - immunology; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35606-6

SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351, and Omicron/BA.1. Mice vaccinated with two doses of Novavax prototype NVX-CoV2373 (rS-WU1) or rS-Beta alone, in combination, or heterologous prime-boost, are protected from challenge. Virus titer is undetectable in lungs in all vaccinated mice, and Th1-skewed cellular responses are observed. We tested sera from a panel of variant spike protein vaccines and find broad neutralization and inhibition of spike:ACE2 binding from the rS-Beta and rS-Delta vaccines against a variety of variants including Omicron. This study demonstrates that rS-Beta vaccine alone or in combination with rS-WU1 induces antibody-and cell-mediated responses that are protective against challenge with SARS-CoV-2 variants and offers broader neutralizing capacity than a rS-WU1 prime/boost regimen alone. Together, these nonhuman primate and murine data suggest a Beta variant booster dose could elicit a broad immune response to fight new and future SARS-CoV-2 variants. Current SARS-CoV-2 variants evade immune responses induced by approved vaccines. In this study, the authors find that a recombinant prefusion-stabilized Beta spike protein vaccine confers broad neutralization capacity in mice and non-human primates as well as protective antibody and immune memory responses.