Chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine is safe and expands humoral and cellular immunity in adults

Respiratory syncytial virus (RSV) causes respiratory infection in annual epidemics, with infants and the elderly at particular risk of developing severe disease and death. However, despite its importance, no vaccine exists. The chimpanzee adenovirus, PanAd3-RSV, and modified vaccinia virus Ankara, MVA-RSV, are replication defective viral vectors encoding the RSV proteins F, N and M2-1 for the induction of humoral and cellular responses. We performed an open-label, doseescalation, phase 1 clinical trial in 42 healthy adults in which four different combinations of prime/boost vaccinations were investigated for safety and immunogenicity, including both intramuscular and intra-nasal administration of the adenoviral vectored vaccine. The vaccines were safe and well tolerated, with the most common reported adverse events being mild injection site reactions. No vaccine-related serious adverse events occurred. RSV neutralising antibody titres rose in response to intramuscular (IM) prime with PanAd3-RSV, and after IM boost for individuals primed by the intra-nasal (IN) route. Circulating anti-F IgG and IgA antibody secreting cells (ASCs) were observed after IM prime and IM boost. RSV-specific T-cell responses were increased after IM PanAd3-RSV prime and were most efficiently boosted by IM MVA-RSV. Correspondence: christopher.green@paediatrics.ox.uk, tel/fax; 0044 +1865 857 420. Competing interests AJP has previously conducted clinical trials of vaccines on behalf of Oxford University funded by GlaxoSmithKline Biologicals SA and ReiThera S.r.l, but does not receive any personal payments from them. AJP is chair of the UK Department of Health’s (DH) Joint Committee on Vaccination and Immunisation (JCVI), but the views expressed in this manuscript do not necessarily represent the views of JCVI or DH. AV, RC, and AN are named inventors on patent applications covering RSV antigen expression system (WO 2012/089833). The remaining authors declare they have no competing interests. Data and materials availability RSV001 was registered with clinicaltrials.gov and EudraCT (ref NCT01805921 and 2011-003589-34 respectively). Clinicaltrials.gov NCT01805921. Europe PMC Funders Group Author Manuscript Sci Transl Med. Author manuscript; available in PMC 2016 February 12. Published in final edited form as: Sci Transl Med. 2015 August 12; 7(300): 300ra126. doi:10.1126/scitranslmed.aac5745. E uope PM C Fuders A uhor M ancripts E uope PM C Fuders A uhor M ancripts IFNγ secretion after boost was from both CD4+ and CD8+ T-cells, without detectable Th2 cytokines that have been previously associated with immune pathogenesis following exposure to RSV after formalin inactivated RSV vaccine. In conclusion, PanAd3-RSV and MVA-RSV are safe and immunogenic in healthy adults. These vaccine candidates warrant further clinical evaluation of efficacy to assess their potential to reduce the burden of RSV disease.