Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques

作者：Katherine McMahan, Frank Wegmann, Malika Aïd, Michaela Sciacca, Jinyan Liu, Nicole P. Hachmann, Jessica Miller, Catherine Jacob-Dolan, Olivia Powers, David Hope, Cindy Wu, Juliana Pereira, Tetyana Murdza, Camille R. Mazurek, Amelia Hoyt, Adrianus C. M. Boon, Meredith E. Davis-Gardner, Mehul S. Suthar, Amanda J. Martinot, Mona Boursiquot, Anthony Cook, Laurent Pessaint, Mark G. Lewis, Hanné Andersen, Jeroen Tolboom, Jan Serroyen, Laura Solforosi, L M M Costes, Roland Zahn, Dan H. Barouch · 发表于：Nature · 年份：2023 · DOI：10.1038/s41586-023-06951-3 · 被引用次数：101 · 研究领域：SARS-CoV-2 and COVID-19 Research、Bacterial Infections and Vaccines、Respiratory viral infections research

Abstract A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants 1,2 , although they still provide protection against severe disease. Enhanced mucosal immunity may be required to block infection and onward transmission. Intranasal administration of current vaccines has proven inconsistent 3–7 , suggesting that alternative immunization strategies may be required. Here we show that intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 challenge. A total of 40 previously immunized rhesus macaques were boosted with a bivalent Ad26 vaccine by the intramuscular, intranasal and intratracheal routes, or with a bivalent mRNA vaccine by the intranasal route. Ad26 boosting by the intratracheal route led to a substantial expansion of mucosal neutralizing antibodies, IgG and IgA binding antibodies, and CD8 + and CD4 + T cell responses, which exceeded those induced by Ad26 boosting by the intramuscular and intranasal routes. Intratracheal Ad26 boosting also led to robust upregulation of cytokine, natural killer, and T and B cell pathways in the lungs. After challenge with a high dose of SARS-CoV-2 BQ.1.1, intratracheal Ad26 boosting provided near-complete protection, whereas the other boosting strategies proved less effective. Protective efficacy correlated best with muc...