Abstract
Background BK-SE36/CpG is a recombinant Plasmodium falciparum vaccine candidate targeting blood-stage parasites. The P. falciparum SE36 protein was expressed in E. coli, adsorbed to aluminium hydroxide gel, and reconstituted with CpG adjuvant. An acceptable safety profile of the BK-SE36/CpG vaccine was previously showed in healthy malaria-naïve Japanese adults. The aim of the Phase Ib study reported here was to assess the safety and immunogenicity in healthy malaria-exposed African adults and children.
Methods A double-blind, randomized, controlled, age de-escalating, clinical trial was conducted in an urban area of Ouagadougou, Burkina Faso. One hundred and thirty-five healthy participants aged 21–45 years, 5–10 years, and 12–24 months were randomized 2:1 to receive three vaccine doses of BK-SE36/CpG (BK) or rabies vaccine. Subjects were monitored within 7 and 28 days following each vaccination for solicited and unsolicited adverse events. Severe and serious adverse events were collected throughout the study duration (12 months). Immune responses were measured at baseline, 28 days after each vaccination, and at trial end.
Results Of the one hundred thirty-five subjects enrolled, one hundred thirty-four received all three scheduled vaccine doses. Five Grade 3 events unrelated to vaccination were reported in three subjects (3%) in the BK arm. Five SAEs reported, all due to severe malaria, were judged unrelated to the study vaccine. BK induced higher mean anti-SE36 antibody titers compared to control, with higher titers post-Dose3 compared to post-Dose2. A stronger immune response was observed in younger cohorts (12–24-month-old > 5–10-year-old > 21–45-year-old). In all cohorts, epitope mapping of sera from BK vaccinees showed predominant reactivity with the synthetic peptides that are lied into intrinsically unstructured regions.
Conclusion The BK-SE36/CpG vaccine was well-tolerated and immunogenic in all age groups. These results pave the way for further proof-of-concept studies with larger cohorts to demonstrate the efficacy of the vaccine.
