Transcriptomic response and immunological responses to chimpanzee adenovirus- and MVA viral-vectored vaccines for RSV in healthy adults

C Green, J McGinley*, C Sande, S Capone, S Makvandi-Nejad, A Vitelli, L Silva-Reyes, S Bibi, C Otasowie, D Sheerin, A Thompson, C Dold, P Klenerman, E Barnes, L Dorrell, C Rollier, A Pollard, D O’Connor

*Corresponding author for this work

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Abstract

Cohorts of healthy younger adults (18–50yrs) and healthy older adults (60–75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses.
Original languageEnglish
Pages (from-to)269–279
Number of pages11
JournalClinical and Experimental Immunology
Volume211
Issue number3
Early online date9 Jan 2023
DOIs
Publication statusPublished - Mar 2023

Bibliographical note

Funding:
The RSV001 clinical trial was funded and sponsored by ReiThera S.r.l. (formerly Okairos S.r.l), which was acquired by GlaxoSmithKline Biologicals SA during the trial. Further funding and support was provided by the NIHR Oxford Biomedical Research and for Charles Sande and Paul Klenerman from the Wellcome Trust (WT 091663MA).

Keywords

  • RSV
  • vaccine
  • transcriptomics
  • human trials
  • antibodies
  • viral vectors

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