Safety and immunogenicity of a purified inactivated Zika virus vaccine candidate in adults primed with a Japanese encephalitis virus or yellow fever virus vaccine in the USA: a phase 1, randomised, double-blind, placebo-controlled clinical trial

• Published in: The Lancet infectious diseases 2023-10, Vol.23 (10), p.1175-1185
• Main Authors: Koren, Michael A, Lin, Leyi, Eckels, Kenneth H, De La Barrera, Rafael, Dussupt, Vincent, Donofrio, Gina, Sondergaard, Erica L, Mills, Kristin T, Robb, Merlin L, Lee, Christine, Adedeji, Oluwaseun, Keiser, Paul B, Curley, Justin M, Copeland, Nathanial K, Crowell, Trevor A, Hutter, Jack N, Hamer, Melinda J, Valencia-Ruiz, Anais, Darden, Janice, Peel, Sheila, Amare, Mihret F, Mebrahtu, Tsedal, Costanzo, Margaret, Krebs, Shelly J, Gromowski, Gregory D, Jarman, Richard G, Thomas, Stephen J, Michael, Nelson L, Modjarrad, Kayvon
• Format: Article
• Language: English
• Subjects: Adult; Adults; Adverse events; Allergies; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antigens; Birth defects; Breast feeding; Clinical trials; Congenital defects; Criteria; Deactivation; Dengue fever; Double-Blind Method; Double-blind studies; Encephalitis; Encephalitis Virus, Japanese; Female; Fever; Global health; Hepatitis; Hepatitis B; Hepatitis C; HIV; Human immunodeficiency virus; Humans; Immune response (humoral); Immunization; Immunogenicity; Immunogenicity, Vaccine; Infectious diseases; Japanese Encephalitis Vaccines - adverse effects; Male; Microbiology; Neurological complications; Pharmacy; Placebos; Priming; Public health; Safety; Seroconversion; Statistical analysis; Vaccines; Vaccines, Inactivated; Vector-borne diseases; Viral Vaccines; Viruses; West Nile virus; Yellow Fever - prevention & control; Yellow Fever Vaccine - adverse effects; Yellow fever virus; Zika Virus; Zika Virus Infection - prevention & control
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(23)00192-5

Zika virus infection is a threat to at-risk populations, causing major birth defects and serious neurological complications. Development of a safe and efficacious Zika virus vaccine is, therefore, a global health priority. Assessment of heterologous flavivirus vaccination is important given co-circulation of Japanese encephalitis virus and yellow fever virus with Zika virus. We investigated the effect of priming flavivirus naive participants with a licensed flavivirus vaccine on the safety and immunogenicity of a purified inactivated Zika vaccine (ZPIV). This phase 1, placebo-controlled, double-blind trial was done at the Walter Reed Army Institute of Research Clinical Trials Center in Silver Spring, MD, USA. Eligible participants were healthy adults aged 18–49 years, with no detectable evidence of previous flavivirus exposure (by infection or vaccination), as measured by a microneutralisation assay. Individuals with serological evidence of HIV, hepatitis B, or hepatitis C infection were excluded, as were pregnant or breastfeeding women. Participants were recruited sequentially into one of three groups (1:1:1) to receive no primer, two doses of intramuscular Japanese encephalitis virus vaccine (IXIARO), or a single dose of subcutaneous yellow fever virus vaccine (YF-VAX). Within each group, participants were randomly assigned (4:1) to receive intramuscular ZPIV or placebo. Priming vaccinations were given 72–96 days before ZPIV. ZPIV was administered either two or three times, at days 0, 28, and 196–234. The primary outcome was occurrence of solicited systemic and local adverse events along with serious adverse events and adverse events of special interest. These data were analysed in all participants receiving at least one dose of ZPIV or placebo. Secondary outcomes included measurement of neutralizing antibody responses following ZPIV vaccination in all volunteers with available post-vaccination data. This trial is registered at ClinicalTrials.gov, NCT02963909. Between Nov 7, 2016, and Oct 30, 2018, 134 participants were assessed for eligibility. 21 did not meet inclusion criteria, 29 met exclusion criteria, and ten declined to participate. 75 participants were recruited and randomly assigned. 35 (47%) of 75 participants were male and 40 (53%) were female. 25 (33%) of 75 participants identified as Black or African American and 42 (56%) identified as White. These proportions and other baseline characteristics were similar between groups. There were no stat