RT Journal Article
SR Electronic
T1 Mucosal vaccination for SARS-CoV-2 elicits superior systemic T central memory function and cross-neutralizing antibodies against variants of concern
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.09.507250
DO 10.1101/2022.09.09.507250
A1 Aled O’Neill
A1 Monica Palanichamy Kala
A1 Tan Chee Wah
A1 Wilfried A.A. Saron
A1 Chinmay Kumar Mantri
A1 Abhay P.S. Rathore
A1 Lin-Fa Wang
A1 Ashley L. St. John
YR 2022
UL http://biorxiv.org/content/early/2022/09/09/2022.09.09.507250.abstract
AB COVID-19 vaccines used in humans are highly effective in limiting disease and death caused by the SARS-CoV-2 virus, yet improved vaccines that provide greater protection at mucosal surfaces, which could reduce break-through infections and subsequent transmission, are still needed. Here we show that intranasal (I.N.) vaccination with the receptor binding domain of Spike antigen of SARS-CoV-2 (S-RBD) in combination with the mucosal adjuvant mastoparan-7 improved systemic T cell responses compared to an equivalent dose of antigen delivered by the sub-cutaneous (S.C.) route, adjuvanted by either M7 or the gold-standard adjuvant, alum. T cell phenotypes induced by I.N. vaccine administration included enhanced polyfunctionality (combined IFN-γ and TNF expression) and greater numbers of T central memory (TCM) cells. These phenotypes were T cell-intrinsic and could be recalled in the lungs and/or brachial LNs upon antigen challenge after adoptive T cell transfer to naïve recipients. Furthermore, mucosal vaccination induced antibody responses that were similarly effective in neutralizing the binding of the parental strain of S-RBD to its ACE2 receptor, but showed greater cross-neutralizing capacity against multiple variants of concern (VOC), compared to S.C. vaccination. These results highlight the role of nasal vaccine administration in imprinting an immune profile associated with long-term T cell retention and diversified neutralizing antibody responses, which could be applied to improve vaccines for COVID-19 and other infectious diseases.Competing Interest StatementThe authors have declared no competing interest.