Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial. (13th November 2017)

• Record Type: Journal Article
• Authors: Leroux-Roels, Geert; Cramer, Jakob P; Mendelman, Paul M; Sherwood, James; Clemens, Ralf; Aerssens, Annelies; De Coster, Ilse; Borkowski, Astrid; Baehner, Frank; Van Damme, Pierre
• Is Part Of: Journal of infectious diseases. Volume 217:Number 4(2018)
• Page Start: 597
• Page End: 607
• Publication Date: 2017-11-13
• Subjects: norovirus -- vaccine -- immunogenicity -- reactogenicity -- adults; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix572
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : Bivalent (GI.1 and GII.4) virus-like particle norovirus candidate vaccine formulations were well tolerated and immunogenic, 1 dose inducing immune responses that persisted up to 1 year, which were not increased by inclusion of monophosphoryl lipid A or administration of a second dose. Abstract: Background: We investigated safety and immunogenicity of 1–2 doses of different bivalent virus-like particle (VLP) norovirus vaccine candidate (NoV) formulations in healthy 18- to 64-year-olds. Methods: On days 1 and 28, participants (n = 420) randomized to 14 equal groups received intramuscular control vaccine (hepatitis A) or 1 of 11 NoV formulations containing varying dosages of GI.1 and GII.4c genotype VLP antigens with aluminum hydroxide [Al(OH)3 ], and 0 μg, 15 μg, or 50 μg monophosphoryl lipid A (MPL). Immunogenicity was assessed on days 1, 28, 56, 208 and 393. Solicited local and systemic reactions were recorded for 7 days, unsolicited adverse events (AEs) until day 56, and serious AEs throughout the trial. Results: All NoV formulations induced similar increases in pan-immunoglobulin, immunoglobulin A, and histo-blood group binding antigen-blocking antibodies by day 56, mostly after 1 dose, that persisted above baseline to day 393. Higher GI.1 content interfered with GII.4c responses, and responses did not benefit from MPL. Overall reactogenicity consisted of mainly mild injection site pain, headache, and fatigue. No vaccine-related serious AEs were reported. Conclusions: All candidate NoV formulations were well tolerated. Overall, 15 μg GI.1/50 μg GII.4c elicited the best balance of immunogenicity with no clear benefit of MPL, and is the candidate formulation being taken forward in clinical development. Clinical Trials Registration: NCT02038907.