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

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  • Additional Information
    • Source:
      Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101647039 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3964 (Electronic) Linking ISSN: 23523964 NLM ISO Abbreviation: EBioMedicine Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Amsterdam] : Elsevier B.V., [2014]-
    • Subject Terms:
      COVID-19 Vaccines* ; COVID-19*/prevention & control; Cricetinae ; Humans ; Animals ; Mice ; Rodentia ; Broadly Neutralizing Antibodies ; SARS-CoV-2 ; Vaccination ; Adjuvants, Immunologic ; Antibodies, Neutralizing ; Antibodies, Viral
    • 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 (T CM ) 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.
      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.)
    • Contributed Indexing:
      Keywords: COVID-19; Mucosal vaccine; SARS-CoV-2; T cell
    • Accession Number:
      0 (COVID-19 Vaccines)
      0 (Broadly Neutralizing Antibodies)
      0 (Adjuvants, Immunologic)
      0 (Antibodies, Neutralizing)
      0 (Antibodies, Viral)
    • Publication Date:
      Date Created: 20231219 Date Completed: 20240122 Latest Revision: 20240122
    • Publication Date:
      20240122
    • Accession Number:
      PMC10772395
    • Accession Number:
      10.1016/j.ebiom.2023.104924
    • Accession Number:
      38113758