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A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Sodiomon B Sirima
  • Benjamin Mordmüller
  • Paul Milligan
  • Ulysse Ateba Ngoa
  • Fred Kironde
  • Frank Atuguba
  • Alfred B Tiono
  • Saadou Issifou
  • Mark Kaddumukasa
  • Oscar Bangre
  • Clare Flach
  • Michael Christiansen
  • Peter Bang
  • Roma Chilengi
  • Søren Jepsen
  • Peter G Kremsner
  • Theisen, Michael

BACKGROUND: GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda.

METHODS: Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL.

RESULTS: A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%).

CONCLUSIONS: GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.

OriginalsprogEngelsk
TidsskriftVaccine
Vol/bind34
Udgave nummer38
Sider (fra-til)4536-4542
Antal sider7
ISSN0264-410X
DOI
StatusUdgivet - aug. 2016

ID: 165010179