First-in-Human Randomized Study to Assess the Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus (RSV) Vaccine Based on Chimpanzee-Adenovirus-155 Viral Vector-Expressing RSV Fusion, Nucleocapsid, and Antitermination Viral Proteins in Healthy Adults.

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

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.

DOI

10.1093/cid/ciz653

Type

Journal article

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Publication Date

05/2020

Volume

70

Pages

2073 - 2081

Addresses

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, United Kingdom.

Keywords

Leukocytes, Mononuclear, Animals, Humans, Pan troglodytes, Adenoviridae, Virion, Nucleocapsid, Respiratory Syncytial Virus Infections, Viral Proteins, Respiratory Syncytial Virus Vaccines, Antibodies, Viral, Adolescent, Adult, Middle Aged, Young Adult, Antibodies, Neutralizing

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