Ad26.COV2.S and SARS-CoV-2 spike protein ferritin nanoparticle vaccine protect against SARS-CoV-2 Omicron BA.5 challenge in macaques
Jingyou Yu, Paul V. Thomas, Michaela Sciacca, Cindy Wu, Jinyan Liu, Xuan He, Jessica Miller, Nicole P. Hachmann, Nehalee Surve, Katherine McMahan, Catherine Jacob-Dolan, Olivia Powers, Kevin Hall, Julia Barrett, David Hope, Camille R. Mazurek, Tetyana Murdza, William C. Chang, Emily S. Golub, Phyllis A. Rees, Caroline E. Peterson, Agnes Hajduczki, Wei‐Hung Chen, Elizabeth J. Martinez, Elizabeth Hussin, Camille Lange, Hua Gong, Gary R. Matyas, Mangala Rao, Mehul S. Suthar, Mona Boursiquot, Anthony Cook, Laurent Pessaint, Mark G. Lewis, Hanné Andersen, Diane L. Bolton, Nelson L. Michael, Michael Joyce, Kayvon Modjarrad, Dan H. Barouch
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines demonstrate reduced protection against acquisition of BA.5 subvariant but are still effective against severe disease. However, immune correlates of protection against BA.5 remain unknown. We report the immunogenicity and protective efficacy of vaccine regimens consisting of the vector-based Ad26.COV2.S vaccine and the adjuvanted spike ferritin nanoparticle (SpFN) vaccine against a high-dose, mismatched Omicron BA.5 challenge in macaques. The SpFNx3 and Ad26 + SpFNx2 regimens elicit higher antibody responses than Ad26x3, whereas the Ad26 + SpFNx2 and Ad26x3 regimens induce higher CD8 T cell responses than SpFNx3. The Ad26 + SpFNx2 regimen elicits the highest CD4 T cell responses. All three regimens suppress peak and day 4 viral loads in the respiratory tract, which correlate with both humoral and cellular immune responses. This study demonstrates that both homologous and heterologous regimens involving Ad26.COV2.S and SpFN vaccines provide robust protection against a mismatched BA.5 challenge in macaques.