Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates
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.
Authors
- Farida Laboune
- Meredith E. Davis-Gardner (ORCID: https://orcid.org/0000-0002-6133-3613)
- Bushra Wali (ORCID: https://orcid.org/0000-0001-9278-8744)
- Danyi Wang (ORCID: https://orcid.org/0009-0008-0820-7037)
- Matthew R. Burnett
- Bob C. Lin (ORCID: https://orcid.org/0000-0002-1373-1406)
- Anna Mychalowych
- David T. Curiel (ORCID: https://orcid.org/0000-0003-3802-6014)
- Mehul S. Suthar (ORCID: https://orcid.org/0000-0002-2686-8380)
- Evan Lamb (ORCID: https://orcid.org/0000-0002-6837-2842)
- Daniel C. Douek (ORCID: https://orcid.org/0000-0001-5575-8634)
- Igor P. Dmitriev (ORCID: https://orcid.org/0000-0001-9206-1975)
- James Brett Case (ORCID: https://orcid.org/0000-0001-7331-5511)
- Barbara J. Flynn (ORCID: https://orcid.org/0000-0001-6276-192X)
- Matthew Gagné (ORCID: https://orcid.org/0000-0001-5526-6162)
- Alan Dodson (ORCID: https://orcid.org/0000-0003-2733-2753)
- Kathryn E. Foulds (ORCID: https://orcid.org/0000-0003-4418-6495)
- Peter D. Kwong (ORCID: https://orcid.org/0000-0003-3560-232X)
- Dillon R. Flebbe
- Mark G. Lewis (ORCID: https://orcid.org/0000-0001-7852-0135)
- Lingshu Wang (ORCID: https://orcid.org/0000-0002-8404-4910)
- Madison Ellis (ORCID: https://orcid.org/0000-0002-0325-5477)
- Martha Nason (ORCID: https://orcid.org/0000-0002-0110-881X)
- Erin Maule
- John-Paul Todd (ORCID: https://orcid.org/0000-0003-1203-3144)
- Leonid Serebryannyy (ORCID: https://orcid.org/0000-0003-0213-1779)
- Robert A. Seder (ORCID: https://orcid.org/0000-0003-3133-0849)
- Josue Marquez
- Serge Zouantchangadou
- Shayne F. Andrew (ORCID: https://orcid.org/0000-0001-7226-7757)
- Michael Diamond (ORCID: https://orcid.org/0000-0002-8791-3165)
- Amy R. Henry
- Laurent Pessaint (ORCID: https://orcid.org/0000-0002-2126-3008)
- Nicole A. Doria‐Rose (ORCID: https://orcid.org/0000-0002-5731-3054)
- Mursal Naisan
- I‐Ting Teng (ORCID: https://orcid.org/0000-0002-4704-7100)
- Yogita Jethmalani (ORCID: https://orcid.org/0000-0003-3422-8356)
- Mario Roederer (ORCID: https://orcid.org/0000-0001-7448-7040)
- Sucheta Godbole (ORCID: https://orcid.org/0000-0002-7564-1748)
- Zohar E. Ziff
- Katelyn Kouneski
- Qiong Zhou (ORCID: https://orcid.org/0009-0007-7515-0256)
- Baoling Ying
- Elena A. Kashentseva
- Sijy O’Dell (ORCID: https://orcid.org/0000-0002-4951-8471)
- Hanné Andersen
- Robin Carroll
- Alex Van Ry
Institutions
- National Institutes of Health (US)
- Emory University (US)
- Washington University in St. Louis (US)
- Bioqual (US)
- National Institute of Allergy and Infectious Diseases (US)
- Children's Healthcare of Atlanta (US)
- Emory National Primate Research Center
Publication Details
- Journal
- Nature Immunology
- Published
- 2024-09-03
- DOI
- https://doi.org/10.1038/s41590-024-01951-5
- Citations
- 35
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 13.62
Funders
- Emory University
- Children's Healthcare of Atlanta
- Moderna
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases