Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial
| Autor: | Frank Baehner, Pierre Van Damme, Astrid Borkowski, James Sherwood, Jakob P Cramer, Ilse De Coster, Geert Leroux-Roels, Paul M. Mendelman, Ralf Clemens, Annelies Aerssens |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male viruses Monophosphoryl Lipid A Pharmacology immunogenicity Antibodies Viral fluids and secretions vaccine adults Immunology and Allergy Medicine Caliciviridae Infections Vaccines Viral Vaccine Immunogenicity Hepatitis A virus diseases Middle Aged Healthy Volunteers Infectious Diseases Female Adult Dose Adolescent Drug-Related Side Effects and Adverse Reactions Genotype Drug Compounding norovirus reactogenicity complex mixtures Injections Intramuscular 03 medical and health sciences Young Adult Major Articles and Brief Reports Double-Blind Method parasitic diseases Humans Adverse effect Biology Immunization Schedule Reactogenicity business.industry Viral Vaccines medicine.disease Clinical trial 030104 developmental biology Antibody Formation Human medicine business |
| Zdroj: | The Journal of Infectious Diseases The journal of infectious diseases |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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