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 evaluated an investigational vaccine against RSV (ChAd155-RSV) using the viral vector chimpanzee-adenovirus-155, encoding RSV fusion (F), nucleocapsid, and transcription antitermination proteins. Methods. Healthy 18-45-year-old adults received ChAd155-RSV, a placebo, or an active control (Bexsero) at Days (D) 0 and 30. An escalation from a low dose (5 x 10(9) viral particles) to a high dose (5 x 10(10) viral particles) occurred after the first 16 participants. Endpoints were solicited/unsolicited and serious adverse events (SAEs), biochemical/hematological parameters, cell-mediated immunogenicity by enzyme-linked immunospot, functional neutralizing antibodies, anti RSV-F immunoglobin (Ig) G, and ChAd155 neutralizing antibodies. Results. There were 7 participants who received the ChAd155-RSV low dose, 31 who received the ChAd155-RSV high dose, 19 who received the placebo, and 15 who received the active control. No dose-related toxicity or attributable SAEs at the 1-year follow-up were observed. The RSV-A neutralizing antibodies geometric mean titer ratios (post/pre-immunization) following a high dose were 2.6 (D30) and 2.3 (D60). The ratio of the fold-rise (D0 to D30) in anti-F IgG over the fold-rise in RSV-A-neutralizing antibodies was 1.01. At D7 after the high dose of the study vaccine, the median frequencies of circulating B-cells secreting anti-F antibodies were 133.3/10(6) (IgG) and 16.7/10(6) (IgA) in peripheral blood mononuclear cells (PBMCs). The median frequency of RSV-F-specific interferon gamma-secreting T-cells after a ChAd155-RSV high dose was 108.3/10(6) PBMCs at D30, with no increase after the second dose. Conclusions. In adults previously naturally exposed to RSV, ChAd155-RSV generated increases in specific humoral and cellular immune responses without raising significant safety concerns.