Highly effective malaria vaccines are crucial to further reduce the burden of malaria. The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) Vaccine protects adults; however, there are insufficient efficacy data in child populations. We aimed to assess the safety and efficacy of the PfSPZ Vaccine in children aged 1–12 years in Gabon.

This randomised, double-blind, placebo-controlled, phase 2 trial was conducted at the Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon. Healthy children were stratified by age (1–2, 3–6, and 7–12 years) and allocated 2:1 by block randomisation to receive 9·0 × 10 ⁵ PfSPZ Vaccine or placebo (normal saline), administered by direct venous inoculation on days 1, 8, and 29. Artemether–lumefantrine was given before the third vaccination to clear latent parasitaemia. The co-primary endpoints were safety, evaluated in the intention-to-treat population by severe adverse events within 7 days (solicited) and 28 days (unsolicited) of vaccination and by serious adverse events; and vaccine efficacy, measured as time to first P falciparum -positive thick blood smear (TBS), 2–26 weeks after immunisation in those who received three vaccinations (ie, the modified intention-to-treat population). The trial was registered at ClinicalTrials.gov , NCT03521973 , and is complete.

Between June 21, 2018, and April 30, 2019, 345 children were assessed for eligibility, of whom 200 were enrolled to the study: 134 were allocated to receive PfSPZ Vaccine and 66 to receive placebo. 192 participants received three vaccinations and comprised the modified intention-to-treat population. Systemic adverse events were reported by 33 (25%) of 134 participants in the vaccine group (47 events) and 15 (23%) of 66 participants in the placebo group (25 events); subjective fever was the most reported event in both groups. Three grade 3 systemic adverse events were reported (two cases of elevated body temperature and one case of subjective fever), all in the placebo group. 32 serious adverse events were reported across 22 study participants, 13 (10%) of 134 in the vaccine group and nine (14%) of 66 in the placebo group, all of which were considered unrelated to the intervention. There were no treatment-related deaths. 25 (19%) of 129 vaccine recipients and 14 (23%) of 63 placebo recipients became TBS-positive for P falciparum at 2–26 weeks after vaccination. The age-stratum-adjusted vaccine efficacy (1 − hazard ratio) was 9% (95% CI −75 to 53; p=0·78).

PfSPZ Vaccine is well tolerated and safe, but it did not prevent P falciparum infection in children in Gabon. Whether presumptive treatment during immunisation or more potent PfSPZ vaccines can establish vaccine efficacy is currently under investigation.

German Center for Infection Research, European and Developing Countries Clinical Trials Partnership, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Sanaria.