학술논문
Novel genetically-modified chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine safely boosts humoral and cellular immunity in healthy older adults.
Document Type
Academic Journal
Author
Green CA; Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom. Electronic address: christopher.green@paediatrics.ox.uk.; Sande CJ; Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Scarselli E; Nouscom Srl, via di Castel Romano 100, 00128 Roma, Italy.; Capone S; ReiThera Srl, Via di Castel Romano 100, 00128 Roma, Italy.; Vitelli A; ReiThera Srl, Via di Castel Romano 100, 00128 Roma, Italy.; Nicosia A; Keires AG, Baumleingasse 18, CH 4051 Basel, Switzerland; CEINGE, Via Gaetano Salvatore 486, 80145 Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.; Silva-Reyes L; Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Thompson AJ; Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; de Lara CM; Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford, Peter Medawar building, Oxford OX1 3SY, United Kingdom.; Taylor KS; Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, United Kingdom.; Haworth K; Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Hutchings CL; Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford, Peter Medawar building, Oxford OX1 3SY, United Kingdom.; Cargill T; Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford, Peter Medawar building, Oxford OX1 3SY, United Kingdom.; Angus B; Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Klenerman P; Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford, Peter Medawar building, Oxford OX1 3SY, United Kingdom.; Pollard AJ; Oxford Vaccine Group, Department of Paediatrics and the NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
Source
Publisher: W.B. Saunders Country of Publication: England NLM ID: 7908424 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2742 (Electronic) Linking ISSN: 01634453 NLM ISO Abbreviation: J Infect Subsets: MEDLINE
Subject
Language
English
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 chimpanzee 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 antibody responses (RSV- and PanAd3-neutralising antibody titres measured by plaque-reduction neutralisation 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 comparable 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 induction of RSV-specific humoral and cellular immunity merits further assessment in providing protection from severe disease.
(Copyright © 2019. Published by Elsevier Ltd.)
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 antibody responses (RSV- and PanAd3-neutralising antibody titres measured by plaque-reduction neutralisation 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 comparable 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 induction of RSV-specific humoral and cellular immunity merits further assessment in providing protection from severe disease.
(Copyright © 2019. Published by Elsevier Ltd.)