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

Autor: L Silva-Reyes, Elisa Scarselli, Alfredo Nicosia, Stefania Capone, Paul Klenerman, Tamsin Cargill, C de Lara, Andrew J. Pollard, Charles J. Sande, Amber J. Thompson, Kathryn Mary Taylor, Claire Hutchings, Brian Angus, Christopher A Green, Alessandra Vitelli, K Haworth
Přispěvatelé: Green, Christopher A., Sande, Charles J., Scarselli, Elisa, Capone, Stefania, Vitelli, Alessandra, Nicosia, Alfredo, Silva-Reyes, Laura, Thompson, Amber J., de Lara, Catherine M., Taylor, Kathryn S., Haworth, Kathryn, Hutchings, Claire L., Cargill, Tamsin, Angus, Brian, Klenerman, Paul, Pollard, Andrew J.
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Viral vectors
Male
0301 basic medicine
Cellular immunity
T-Lymphocytes
viruses
Respiratory syncytial virus
Antibodies
Viral
Elderly
0302 clinical medicine
Medicine
030212 general & internal medicine
Older adult
B-Lymphocytes
Drug Carriers
Immunity
Cellular
Vaccines
Synthetic
Immunogenicity
ELISPOT
virus diseases
Respiratory infection
respiratory system
Middle Aged
Healthy Volunteers
Vaccination
Infectious Diseases
Older adults
Respiratory syncytial viru
Female
Adult
Microbiology (medical)
Adolescent
Drug-Related Side Effects and Adverse Reactions
030106 microbiology
Vaccinia virus
Respiratory Syncytial Virus Infections
Injections
Intramuscular
Article
Mastadenovirus
Young Adult
03 medical and health sciences
Viral vector
Immune system
Immunity
Respiratory Syncytial Virus Vaccines
Humans
Antibody-Producing Cells
Administration
Intranasal
Immunization Schedule
Aged
business.industry
Vaccine trial
Antibodies
Neutralizing
Immunity
Humoral
Respiratory Syncytial Virus
Human
Immunology
business
Vaccine
Zdroj: The Journal of Infection
ISSN: 1532-2742
0163-4453
Popis: Highlights • There is no licensed vaccine to prevent severe disease caused by respiratory syncytial virus (RSV) infection. • RSV is a major cause of hospitalisation and death in the elderly. • The novel viral-vectored vaccines PanAd3-RSV and MVA-RSV appeared safe and boosted both humoral and cellular RSV-specific immune responses in healthy older adults. • The magnitude of immune responses to vaccination appeared similar to what was observed in younger adults.
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.
Databáze: OpenAIRE
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