Safety and effectiveness of a recombinant hepatitis E vaccine in women of childbearing age in rural Bangladesh: a phase 4, double-blind, cluster-randomised, controlled trial.

Autor:	Zaman K; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh., Julin CH; Division of Infection Control, Norwegian Institute of Public Health, Oslo, Norway., Aziz AB; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; International Vaccine Institute, Seoul, South Korea., Stene-Johansen K; Division of Infection Control, Norwegian Institute of Public Health, Oslo, Norway., Yunus M; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh., Qadri F; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh., Gurley ES; Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA., Sandbu S; Division of Infection Control, Norwegian Institute of Public Health, Oslo, Norway., Øverbø J; Division of Infection Control, Norwegian Institute of Public Health, Oslo, Norway., Dembinski JL; Division of Infection Control, Norwegian Institute of Public Health, Oslo, Norway., Laake I; Division of Infection Control, Norwegian Institute of Public Health, Oslo, Norway., Bhuiyan TR; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh., Rahman M; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh., Haque W; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh., Khanam M; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh., Clemens JD; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh; Jonathan and Karin Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA., Dudman S; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Oslo University Hospital, Oslo, Norway. Electronic address: susannmg@medisin.uio.no.
Jazyk:	angličtina
Zdroj:	The Lancet. Global health [Lancet Glob Health] 2024 Aug; Vol. 12 (8), pp. e1288-e1299.
DOI:	10.1016/S2214-109X(24)00192-X
Abstrakt:	Background: Hepatitis E virus (HEV) leads to high mortality in pregnant women in low-income countries. We aimed to evaluate the safety of a HEV vaccine and its effectiveness in preventing hepatitis E during pregnancy. Methods: In this phase 4, double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomised 1:1 to receive HEV239 (a recombinant HEV vaccine) or a control vaccine (Hepa-B, a hepatitis B vaccine), using block randomisation with random number tables and blocks of size eight, stratified by cluster population size. Eligible non-pregnant women (aged 16-39 years) were vaccinated intramuscularly on day 0, at 1 month, and at 6 months, and followed up for 2 years after the last immunisation. The primary endpoint was hepatitis E in the pregnant, per-protocol population (those who received all three doses within 2 days of the scheduled dates), while safety was a secondary endpoint, assessed in the intention-to-treat (ITT) population (participants who received at least one dose). Solicited adverse events were recorded for the first 7 days after each dose, and unsolicited events until 2 years after a participant's final dose. Pregnancy-related safety outcomes were assessed in the pregnant ITT population. This study is registered with ClinicalTrials.gov (NCT02759991). Findings: Between Oct 2, 2017, and Feb 28, 2019, 19 460 participants were enrolled and received either HEV239 (9478 [48·7%] participants, 33 clusters) or Hepa-B (9982 [51·3%] participants, 34 clusters), of whom 17 937 (92·2%) participants received three doses and 17 613 (90·5%) were vaccinated according to protocol (8524 [48·4%] in the HEV239 group and 9089 [51·6%] in the control group). No pregnant participants were confirmed to have hepatitis E in either treatment group. HEV239 showed a mild safety profile, similar to Hepa-B, with no difference in the proportion of solicited adverse events between groups and no severe solicited events. Pain was the most common local symptom (1215 [12·8%] HEV239 recipients and 1218 [12·2%] Hepa-B recipients) and fever the most common systemic symptom (141 [1·5%] HEV239 recipients and 145 [1·5%] Hepa-B recipients). None of the serious adverse events or deaths were vaccine related. Among pregnant participants, the HEV239 group had a higher risk of miscarriage (136 [5·7%] of 2407 pregnant participants) compared with the control group (102 [3·9%] of 2604; adjusted odds ratio 1·54 [95% CI 1·15-2·08]). Interpretation: The effectiveness of HEV239 in pregnant women remains uncertain. HEV239 was safe and well tolerated in non-pregnant women, but findings regarding miscarriage warrant further investigation. Funding: Research Council of Norway; Innovax. Competing Interests: Declaration of interests We declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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