Protective efficacy of peptides from Plasmodium vivax circumsporozoite protein

Vivax malaria is a major cause of morbidity and mortality worldwide, with several million clinical cases per year and 2.5 billion at risk of infection. A vaccine is urgently needed but the most advanced malaria vaccine, VMP001, confers only very low levels of protection against vivax malaria challenge in humans. VMP001 is based on the circumsporozoite protein (CSP) of Plasmodium vivax. Here a virus-like particle, Qβ, is used as a platform to generate very high levels of antibody against peptides from PvCSP in mice, in order to answer questions important to further development of P. vivax CSP (PvCSP) vaccines. Minimal peptides from the VK210 and VK247 allelic variants of PvCSP are found to be highly protective as Qβ-peptide vaccines, using transgenic P. berghei parasites expressing the homologous PvCSP allelic variant. A target of neutralising antibodies within the nonamer unit repeat of VK210, AGDR, is found, as a Qβ-peptide vaccine, to provide partial protection against malaria challenge, and enhances protective efficacy when combined with full-length PvCSP vaccination. A truncated form of PvCSP, missing the N-terminal domain, is found to confer much higher levels of protective efficacy than full-length PvCSP. Peptides derived from highly conserved areas of PvCSP, RI and RII, are found not to confer protective efficacy as Qβ-peptide vaccines.