Mucosal SARS-CoV-2 vaccination of rodents elicits superior systemic T central memory function and cross-neutralising antibodies against variants of concern

O'Neill, A and Mantri, CK and Tan, CW and Saron, WAA and Nagaraj, SK and Kala, MP and Joy, CM and Rathore, APS and Tripathi, S and Wang, L-F and St John, AL (2024) Mucosal SARS-CoV-2 vaccination of rodents elicits superior systemic T central memory function and cross-neutralising antibodies against variants of concern. In: eBioMedicine, 99 .

PDF ebi_med_99_2024.pdf - Published Version Restricted to Registered users only Download (4MB) | Request a copy

Abstract

Background: 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. Methods: Here we tested an 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 compared with the sub-cutaneous (S.C.) route, adjuvanted by either M7 or the gold-standard adjuvant, alum, in mice, for immunological read-outs. The same formulation delivered I.N. or S.C. was tested in hamsters to assess efficacy. Findings: I.N. vaccination improved systemic T cell responses compared to an equivalent dose of antigen delivered S.C. and 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 neutralising the binding of the parental strain of S-RBD to its ACE2 receptor, but showed greater cross-neutralising capacity against multiple variants of concern (VOC), compared to S.C. vaccination. I.N. vaccination provided significant protection from lung pathology compared to unvaccinated animals upon challenge with homologous and heterologous SARS-CoV-2 strains in a hamster model. Interpretation: These results highlight the role of nasal vaccine administration in imprinting an immune profile associated with long-term T cell retention and diversified neutralising antibody responses, which could be applied to improve vaccines for COVID-19 and other infectious diseases. Funding: This study was funded by Duke-NUS Medical School, the Singapore Ministry of Education, the National Medical Research Council of Singapore and a DBT-BIRAC Grant. © 2023 The Author(s)

Item Type:	Journal Article
Publication:	eBioMedicine
Publisher:	Elsevier B.V.
Additional Information:	The copyright for this article belongs to Publisher.
Keywords:	aluminum potassium sulfate; broadly neutralizing antibody; gamma interferon; ketamine; mastoparan; recombinant protein; recombinant s rbd protein; tumor necrosis factor; unclassified drug; xylazine; broadly neutralizing antibody; immunological adjuvant; neutralizing antibody; SARS-CoV-2 vaccine; virus antibody, adjuvant therapy; adoptive transfer; animal cell; animal experiment; antibody response; Article; controlled study; coronavirus disease 2019; drug overdose; enzyme linked immunosorbent assay; flow cytometry; histopathology; lung; male; memory cell; mouse; nonhuman; phenotype; protein domain; real time reverse transcription polymerase chain reaction; receptor binding; Severe acute respiratory syndrome coronavirus 2; Syrian hamster; T lymphocyte; T lymphocyte activation; vaccination; variant of concern; virus neutralization; animal; coronavirus disease 2019; hamster; human; rodent; vaccination, Adjuvants, Immunologic; Animals; Antibodies, Neutralizing; Antibodies, Viral; Broadly Neutralizing Antibodies; COVID-19; COVID-19 Vaccines; Cricetinae; Humans; Mice; Rodentia; SARS-CoV-2; Vaccination
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	01 Mar 2024 09:23
Last Modified:	01 Mar 2024 09:23
URI:	https://eprints.iisc.ac.in/id/eprint/83986

Actions (login required)

View Item