RT Journal Article
SR Electronic
T1 An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.23.517678
DO 10.1101/2022.11.23.517678
A1 Weizhong Li
A1 Tao Wang
A1 Arunraj M. Rajendrakumar
A1 Gyanada Acharya
A1 Zizhen Miao
A1 Berin P. Varghese
A1 Hailiang Yu
A1 Bibek Dhakal
A1 Tanya LeRoith
A1 Wenbin Tuo
A1 Xiaoping Zhu
YR 2022
UL http://biorxiv.org/content/early/2022/11/24/2022.11.23.517678.abstract
AB SARS-CoV-2 and its variants cause COVID-19, which is primarily transmitted through droplets and airborne aerosols. To prevent viral infection and reduce viral spread, vaccine strategies must elicit protective immunity in the airways. FcRn transfers IgG across epithelial barriers; we explore FcRn-mediated respiratory delivery of SARS-CoV-2 spike (S). A monomeric IgG Fc was fused to a stabilized S protein; the resulting S-Fc bound to S-specific antibodies (Ab) and FcRn. A significant increase in Ab responses was observed following the intranasal immunization of mice with S-Fc formulated in CpG as compared to the immunization with S alone or PBS. Furthermore, we intranasally immunize adult or aged mice and 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, including Delta and Omicron variants. Intranasal immunization also significantly reduced viral transmission between immunized and naive hamsters. Protection was mediated by nasal IgA, serum-neutralizing Abs, tissue-resident memory T cells, and bone marrow S-specific plasma cells. Hence FcRn delivers an S-Fc antigen effectively into the airway and induces protection against SARS-CoV-2 infection and transmission. Based on these findings, FcRn-targeted non-invasive respiratory immunizations are superior strategies for preventing highly contagious respiratory viruses from spreading.Competing Interest StatementThe authors have declared no competing interest.