Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates

Matthew Gagne, Barbara J. Flynn, Shayne F. Andrew, Josue Marquez, Dillon R. Flebbe, Anna Mychalowych, Evan Lamb, Meredith E. Davis-Gardner, Matthew R. Burnett, Leonid A. Serebryannyy, Bob C. Lin, Zohar E. Ziff, Erin Maule, Robin Carroll, Mursal Naisan, Yogita Jethmalani, Laurent Pessaint, John Paul M. Todd, Nicole A. Doria-Rose, James Brett CaseIgor P. Dmitriev, Elena A. Kashentseva, Baoling Ying, Alan Dodson, Katelyn Kouneski, Sijy O’Dell, Bushra Wali, Madison Ellis, Sucheta Godbole, Farida Laboune, Amy R. Henry, I. Ting Teng, Danyi Wang, Lingshu Wang, Qiong Zhou, Serge Zouantchangadou, Alex Van Ry, Mark G. Lewis, Hanne Andersen, Peter D. Kwong, David T. Curiel, Mario Roederer, Martha C. Nason, Kathryn E. Foulds, Mehul S. Suthar, Michael S. Diamond, Daniel C. Douek, Robert A. Seder

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1–BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2.

Original languageEnglish
Pages (from-to)1913-1927
Number of pages15
JournalNature immunology
Volume25
Issue number10
DOIs
StatePublished - Oct 2024

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