Novel genetically-modified chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine safely boosts humoral and cellular immunity in healthy older adults

Research output: Contribution to journalArticle

Authors

  • Charles Sande
  • Elisa Scarselli
  • Stefania Capone
  • Alessandra Vitelli
  • Alfredo Nicosia
  • Laura Silva-Reyes
  • Amber Thompson
  • Catherine de Lara
  • Kathryn Taylor
  • Kathryn Haworth
  • Claire Hutchings
  • Tamsin Cargill
  • Brian Angus
  • Paul Klenerman
  • Andrew Pollard

External organisations

  • Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
  • Nouscom Srl
  • ReiThera Srl
  • Kieres AG
  • CIENGE
  • University of Naples
  • Nuffield Department of Primary Care Health Sciences
  • Nuffield Department of Clinical Medicine

Abstract

Objectives: Respiratory syncytial virus (RSV) causes respiratory infection across the world, with infants and the elderly at particular risk of developing severe disease and death. The replication-defective chim- panzee adenovirus (PanAd3-RSV) and modified vaccinia virus Ankara (MVA-RSV) vaccines were shown to be safe and immunogenic in young healthy adults. Here we report an extension to this first-in-man vaccine trial to include healthy older adults aged 60–75 years.

Methods: We evaluated the safety and immunogenicity of a single dose of MVA-RSV given by intra- muscular (IM) injection (n = 6), two doses of IM PanAd3-RSV given 4-weeks apart (n = 6), IM PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n=6), intra-nasal (IN) spray of PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n=6), or no vaccine (n=6). Safety measures included all adverse events within one week of vaccination and blood monitoring. Immunogenicity measures included serum anti- body responses (RSV- and PanAd3-neutralising antibody titres measured by plaque-reduction neutrali- sation and SEAP assays, respectively), peripheral B-cell immune responses (frequencies of F-specific IgG and IgA antibody secreting cells and memory B-cells by ex vivo and cultured dual-colour ELISpot assays respectively), and peripheral RSV-specific T-cell immune responses (frequencies of IFNγ -producing T-cells by ex vivo ELISpot and CD4+/CD8+/Tfh-like cell frequencies by ICS/FACS assay).

Results: The vaccines were safe and well tolerated. Compared with each individual baseline immunity the mean fold-changes in serum RSV-neutralising antibody, appearance and magnitude of F-specific IgG and IgA ASCs and expansion of CD4+/CD8+ IFNγ-producing T-cells in peripheral circulation were com- parable to the results seen from younger healthy adults who received the same vaccine combination and dose. There were little/no IgA memory B-cell responses in younger and older adults. Expansion of IFNγ- producing T-cells was most marked in older adults following IM prime, with balanced CD4+ and CD8+ T cell responses. The RSV-specific immune responses to vaccination did not appear to be attenuated in the presence of PanAd3 (vector) neutralising antibody.

Conclusions: PanAd3-RSV and MVA-RSV was safe and immunogenic in older adults and the parallel in- duction of RSV-specific humoral and cellular immunity merits further assessment in providing protection from severe disease.

Details

Original languageEnglish
Pages (from-to)382-392
Number of pages11
JournalJournal of Infection
Volume78
Issue number5
Early online date8 Feb 2019
Publication statusPublished - May 2019
Externally publishedYes

Keywords

  • Elderly, Older adults, Respiratory syncytial virus, Vaccine, Viral vectors