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Abstract
BackgroundRespiratory 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.MethodsHealthy 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 × 109 viral particles) to a high dose (5 × 1010 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.ResultsThere 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 133.3/106 (IgG) and 16.7/106 (IgA) in peripheral blood mononuclear cells (PBMCs). The median frequency of RSV-F–specific interferon γ–secreting T-cells after a ChAd155-RSV high dose was 108.3/106 PBMCs at D30, with no increase after the second dose.ConclusionsIn adults previously naturally exposed to RSV, ChAd155-RSV generated increases in specific humoral and cellular immune responses without raising significant safety concerns.Clinical Trials RegistrationNCT02491463.
Highlights
Respiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality
In adults previously naturally exposed to RSV, chimpanzee-adenovirus-155 vaccine (ChAd155)-RSV generated increases in specific humoral and cellular immune responses without raising significant safety concerns
The global incidence of respiratory syncytial virus (RSV)associated acute lower respiratory tract infections in 2015 was estimated at 33 million cases in children younger than 5 years, with 10% requiring hospital admission and with up to 59 600 deaths, most of which occurred in developing countries [1]
Summary
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 × 109 viral particles) to a high dose (5 × 1010 viral particles) occurred after the first 16 participants. The vaccination regimen was 2 intramuscular injections of 5 x 109 (low dose [LD]; ChAd155-RSV-LD group) or 5 × 1010 (high dose [HD]; ChAd155-RSV-HD group) viral particles in the deltoid of the nondominant arm, according to a 0, 1-month schedule (see Supplementary Methods for the determination of viral particle concentration). The use of a group B meningococcal vaccine, 4CMenB (Bexsero, GSK), was included as an active control. This was administered at the same 0, 1-month schedule, allowing the maintenance of blinding throughout the trial
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