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.
Cicconi P., Jones C., Sarkar E., Reyes LS., Klenerman P., de Lara C., Hutchings C., Moris P., Janssens M., Fissette LA., Picciolato M., Leach A., Lopez AG., Dieussaert I., Snape MD.
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.