First-in-human randomized study to assess the safety and immunogenicity of an investigational respiratory syncytial virus (RSV) vaccine based on ChAd155 viral vector expressing RSV viral proteins F, N and M2-1 in healthy adults.

BACKGROUND:Respiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality. This phase I, randomized, observer-blind, placebo- and active-controlled study (NCT02491463) evaluated an investigational vaccine against RSV (ChAd155-RSV) using the viral vector chimpanzee-adenovirus-155, encoding RSV fusion (F), nucleocapsid and transcription anti-termination proteins. METHODS:Healthy 18-45-year-old adults received ChAd155-RSV, placebo or active control (Bexsero), at day (D) 0 and D30. Escalation from low dose (5x109 viral particles) to high dose (5x1010 viral particles) occurred after the first 16 participants. Endpoints were solicited/unsolicited and serious adverse events (SAEs), biochemical/hematological parameters, cell-mediated immunogenicity by ELISpot, functional neutralizing antibody , anti RSV-F-IgG, and ChAd155 neutralizing antibodies. RESULTS:Seven participants received ChAd155-RSV low dose, 31 ChAd155-RSV high dose, 19 placebo and 15 active control. No dose-related toxicity or attributable SAEs at 1-year follow-up were observed. The RSV-A- neutralizing antibodies geometric mean titer ratios (post/pre-immunisation) following high dose were 2.6 (D30) and 2.3 (D60). The ratio of the fold-rise (D0 to D30) in anti-F IgG over fold-rise in RSV-A neutralising antibodies was 1.01. At D7 after the high dose of the study vaccine, median frequencies of circulating B-cells secreting anti-F antibodies were 133.3/106 (IgG) and 16.7/106 (IgA) PBMCs. Median frequency of RSV-F specific IFN-γ secreting T-cells after ChAd155-RSV high dose was 108.3/106 PBMCs at D30, with no increase after the second dose. CONCLUSIONS:In adults previously naturally exposed to RSV, ChAd155-RSV generates increases in specific humoral and cellular immune response without raising significant safety concerns.