An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission

Weizhong Li, Tao Wang, Arunraj M. Rajendrakumar, Gyanada Acharya, Zizhen Miao, Berin P. Varghese, Hailiang Yu, Bibek Dhakal, Tanya LeRoith, Athira Karunakaran, Wenbin Tuo and Xiaoping Zhu ()
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Weizhong Li: University of Maryland
Tao Wang: University of Maryland
Arunraj M. Rajendrakumar: University of Maryland
Gyanada Acharya: University of Maryland
Zizhen Miao: University of Maryland
Berin P. Varghese: University of Maryland
Hailiang Yu: University of Maryland
Bibek Dhakal: University of Maryland
Tanya LeRoith: Virginia Tech University
Athira Karunakaran: United States Department of Agriculture
Wenbin Tuo: United States Department of Agriculture
Xiaoping Zhu: University of Maryland

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract SARS-CoV-2 is primarily transmitted through droplets and airborne aerosols, and in order to prevent infection and reduce viral spread vaccines should elicit protective immunity in the airways. The neonatal Fc receptor (FcRn) transfers IgG across epithelial barriers and can enhance mucosal delivery of antigens. Here we explore FcRn-mediated respiratory delivery of SARS-CoV-2 spike (S). A monomeric IgG Fc was fused to a stabilized spike; the resulting S-Fc bound to S-specific antibodies and FcRn. Intranasal immunization of mice with S-Fc and CpG significantly induced antibody responses compared to the vaccination with S alone or PBS. Furthermore, we intranasally immunized mice or hamsters with S-Fc. A significant reduction of virus replication in nasal turbinate, lung, and brain was observed following nasal challenges with SARS-CoV-2 and its variants. Intranasal immunization also significantly reduced viral airborne transmission in hamsters. Nasal IgA, neutralizing antibodies, lung-resident memory T cells, and bone-marrow S-specific plasma cells mediated protection. Hence, FcRn delivers an S-Fc antigen effectively into the airway and induces protection against SARS-CoV-2 infection and transmission.

Date: 2023
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DOI: 10.1038/s41467-023-42796-0

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