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.