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

Katherine McMahan, Frank Wegmann, Malika Aid, 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 Davis-Gardner, Mehul S. Suthar, Amanda J. Martinot, Mona Boursiquot, Anthony Cook, Laurent Pessaint, Mark G. Lewis, Hanne Andersen, Jeroen Tolboom, Jan Serroyen, Laura Solforosi, Lea M. M. Costes, Roland C. Zahn and Dan H. Barouch ()
Additional contact information
Katherine McMahan: Beth Israel Deaconess Medical Center
Frank Wegmann: Janssen Vaccines and Prevention
Malika Aid: Beth Israel Deaconess Medical Center
Michaela Sciacca: Beth Israel Deaconess Medical Center
Jinyan Liu: Beth Israel Deaconess Medical Center
Nicole P. Hachmann: Beth Israel Deaconess Medical Center
Jessica Miller: Beth Israel Deaconess Medical Center
Catherine Jacob-Dolan: Beth Israel Deaconess Medical Center
Olivia Powers: Beth Israel Deaconess Medical Center
David Hope: Beth Israel Deaconess Medical Center
Cindy Wu: Beth Israel Deaconess Medical Center
Juliana Pereira: Beth Israel Deaconess Medical Center
Tetyana Murdza: Beth Israel Deaconess Medical Center
Camille R. Mazurek: Beth Israel Deaconess Medical Center
Amelia Hoyt: Beth Israel Deaconess Medical Center
Adrianus C. M. Boon: Washington University School of Medicine
Meredith Davis-Gardner: Emory School of Medicine
Mehul S. Suthar: Emory School of Medicine
Amanda J. Martinot: Tufts University Cummings School of Veterinary Medicine
Mona Boursiquot: Bioqual
Anthony Cook: Bioqual
Laurent Pessaint: Bioqual
Mark G. Lewis: Bioqual
Hanne Andersen: Bioqual
Jeroen Tolboom: Janssen Vaccines and Prevention
Jan Serroyen: Janssen Vaccines and Prevention
Laura Solforosi: Janssen Vaccines and Prevention
Lea M. M. Costes: Janssen Vaccines and Prevention
Roland C. Zahn: Janssen Vaccines and Prevention
Dan H. Barouch: Beth Israel Deaconess Medical Center

Nature, 2024, vol. 626, issue 7998, 385-391

Abstract: Abstract A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants1,2, 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 inconsistent3–7, 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 mucosal humoral and cellular immune responses. These data demonstrate that these immunization strategies induce robust mucosal immunity, suggesting the feasibility of developing vaccines that block respiratory viral infections.

Date: 2024
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DOI: 10.1038/s41586-023-06951-3

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