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

Abstract

s u m m a r yObjectives: 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 intramuscular (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 IFN γ -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 + IFN γ -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 IFN γproducing 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.

Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial

“…12 However, our results are consistent with previous studies of adenovirus-vector-based vaccines against respiratory pathogens that evoke humoral and T-cell responses in older adults, including a human adenovirusvectored respiratory syncytial virus (RSV) vaccine 29 and a simian adenovirus-vectored RSV vaccine. 30 Our results with ChAdOx1 nCoV-19 are also consistent with those of a ChAdOx1-vectored vaccine against influenza that showed good immunogenicity in adults older than 50 years. 22 Notably, the anti-spike antibody responses in our study increased after a boost vaccination at an interval of 1 month but the neutralising anti-vector antibody responses did not.…”

The Long Road Toward COVID-19 Herd Immunity: Vaccine Platform Technologies and Mass Immunization Strategies

“…Imophoron's (Bristol, UK) in collaboration with University of Bristol (Bristol, UK) is using the ADDomer vaccine platform, which is an adenovirus-derived multimeric protein-based self-assembling nanoparticle scaffold engineered to facilitate plug-and-play display of multiple immunogenic epitopes from pathogens, and it has been tested against Chikungunya infection ( 142 ). ReiThera (Rome, Italy), LEUKOCARE (Munich, Germany), and Univercells (Brussels, Belgium) are developing a vaccine candidate based on ReiThera's simian adenoviral vector with strong immunological potency ( 143 , 144 ) and Univercells's NevoLine™ biomanufacturing platform for scale up. GeoVax's (Atlanta, GE, USA) MVA platform technology has the advantage of being a live replication-competent vector in avian cells for manufacturing, yet replication-deficient in mammalian cells upon vaccination, and it was found to protect against Lassa fever virus in mice ( 134 ) and Ebola virus in NHPs ( 135 ).…”

The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV

“…MVA vectored vaccines have been shown to boost the magnitude of adenoviral vaccine-induced T cell responses to several immunogens in mice [34][35][36] and humans [8,[37][38][39][40][41]. We therefore designed an MVA encoding SIi-CP mut TPA-S (sh) for use in a heterologous boost regimen following ChAdOx1-SP-SIi-CP mut TPA-S (sh) prime vaccination.…”