Vaccine protection against the SARS-CoV-2 Omicron variant in macaques

• Published in: Cell Vol. 185; no. 9; pp. 1549 - 1555.e11
• Main Authors: Chandrashekar, Abishek, Yu, Jingyou, McMahan, Katherine, Jacob-Dolan, Catherine, Liu, Jinyan, He, Xuan, Hope, David, Anioke, Tochi, Barrett, Julia, Chung, Benjamin, Hachmann, Nicole P., Lifton, Michelle, Miller, Jessica, Powers, Olivia, Sciacca, Michaela, Sellers, Daniel, Siamatu, Mazuba, Surve, Nehalee, VanWyk, Haley, Wan, Huahua, Wu, Cindy, Pessaint, Laurent, Valentin, Daniel, Van Ry, Alex, Muench, Jeanne, Boursiquot, Mona, Cook, Anthony, Velasco, Jason, Teow, Elyse, Boon, Adrianus C.M., Suthar, Mehul S., Jain, Neharika, Martinot, Amanda J., Lewis, Mark G., Andersen, Hanne, Barouch, Dan H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.04.2022; The Authors. Published by Elsevier Inc
• Subjects: Ad26COVS1 - administration & dosage; Ad26COVS1 - immunology; Animals; antibodies; Antibodies, Neutralizing; Antibodies, Viral; BNT162 Vaccine - administration & dosage; BNT162 Vaccine - immunology; CD8-positive T-lymphocytes; COVID-19 - immunology; COVID-19 - prevention & control; Macaca; macaque; nose; Omicron; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; T-Lymphocytes - immunology; vaccines; viruses; macaque; SARS-CoV-2; Omicron
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2022.03.024

The rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. In this study, we show that the mRNA-based BNT162b2 vaccine and the adenovirus-vector-based Ad26.COV2.S vaccine provide robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in cynomolgus macaques. We vaccinated 30 macaques with homologous and heterologous prime-boost regimens with BNT162b2 and Ad26.COV2.S. Following Omicron challenge, vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs. However, 4 vaccinated animals that had moderate Omicron-neutralizing antibody titers and undetectable Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Moreover, virologic control correlated with both antibody and T cell responses. These data suggest that both humoral and cellular immune responses contribute to vaccine protection against a highly mutated SARS-CoV-2 variant. [Display omitted] •Ad26.COV2.S and BNT162b2 led to rapid virologic control following Omicron challenge•Both Omicron-specific antibodies and T cells contributed to protection•Virologic failure correlated with moderate antibodies and negligible CD8+ T cells Heterologous as well as homologous prime-boosting with the mRNA vaccine BNT162b2 and adenovirus-vector-based Ad26.COV2.S vaccine provides robust protection against SARS-CoV-2 Omicron in cynomolgus macaques, with both humoral and cellular immune responses being critical for overall protection.