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Mucosal Vaccine-induced Cross-reactive CD8 T Cells Protect Against SARS-CoV-2 XBB.1.5 Respiratory Tract Infection

Abstract

A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced by monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect in passive transfer experiments, mucosal antibody and cross-reactive memory T cell responses were robust, and protection was evident against WA1/2020 D614G and Omicron variants BQ.1.1 and XBB.1.5 in mice and hamsters. However, depletion of memory CD8 T cells before XBB.1.5 challenge resulted in loss of protection against upper and lower respiratory tract infection. Thus, nasally delivered vaccines stimulate mucosal immunity against emerging SARS-CoV-2 strains, and cross-reactive memory CD8 T cells mediate protection against lung infection by antigenically distant strains in the setting of low serum levels of cross-reactive neutralizing antibodies.

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References
1.
Polack F, Thomas S, Kitchin N, Absalon J, Gurtman A, Lockhart S . Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020; 383(27):2603-2615. PMC: 7745181. DOI: 10.1056/NEJMoa2034577. View

2.
Baden L, El Sahly H, Essink B, Kotloff K, Frey S, Novak R . Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020; 384(5):403-416. PMC: 7787219. DOI: 10.1056/NEJMoa2035389. View

3.
Knoll M, Wonodi C . Oxford-AstraZeneca COVID-19 vaccine efficacy. Lancet. 2020; 397(10269):72-74. PMC: 7832220. DOI: 10.1016/S0140-6736(20)32623-4. View

4.
Regev-Yochay G, Gonen T, Gilboa M, Mandelboim M, Indenbaum V, Amit S . Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron. N Engl J Med. 2022; 386(14):1377-1380. PMC: 9006792. DOI: 10.1056/NEJMc2202542. View

5.
Link-Gelles R, Ciesla A, Roper L, Scobie H, Ali A, Miller J . Early Estimates of Bivalent mRNA Booster Dose Vaccine Effectiveness in Preventing Symptomatic SARS-CoV-2 Infection Attributable to Omicron BA.5- and XBB/XBB.1.5-Related Sublineages Among Immunocompetent Adults - Increasing Community Access to.... MMWR Morb Mortal Wkly Rep. 2023; 72(5):119-124. PMC: 9927070. DOI: 10.15585/mmwr.mm7205e1. View