Mucosal SARS-CoV-2 vaccination of rodents elicits superior systemic T central memory function and cross-neutralising antibodies against variants of concern.
Autor: | O'Neill A; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 169857, Singapore., Mantri CK; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 169857, Singapore., Tan CW; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 169857, Singapore; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117545, Singapore., Saron WAA; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 169857, Singapore., Nagaraj SK; Centre for Infectious Disease Research, Microbiology and Cell Biology Department, Indian Institute of Science, Bengaluru, 560012, India., Kala MP; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 169857, Singapore., Joy CM; Centre for Infectious Disease Research, Microbiology and Cell Biology Department, Indian Institute of Science, Bengaluru, 560012, India., Rathore APS; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 169857, Singapore; Department of Pathology, Duke University Medical Centre, Durham, North Carolina, 27705, USA., Tripathi S; Centre for Infectious Disease Research, Microbiology and Cell Biology Department, Indian Institute of Science, Bengaluru, 560012, India., Wang LF; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 169857, Singapore; SingHealth Duke-NUS Global Health Institute, Singapore., St John AL; Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, 169857, Singapore; Department of Pathology, Duke University Medical Centre, Durham, North Carolina, 27705, USA; SingHealth Duke-NUS Global Health Institute, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: ashley.st.john@duke-nus.edu.sg. |
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Jazyk: | angličtina |
Zdroj: | EBioMedicine [EBioMedicine] 2024 Jan; Vol. 99, pp. 104924. Date of Electronic Publication: 2023 Dec 18. |
DOI: | 10.1016/j.ebiom.2023.104924 |
Abstrakt: | 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 (T 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. Competing Interests: Declaration of interests ALS is an inventor on a patent relating to mucosal vaccination against COVID-19. LFW and TCW are co-inventors on a patent for the sVNT assay and receive royalties from the cPass kit. (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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