Development of a Plasmodium berghei transgenic parasite expressing the full-length Plasmodium vivax circumsporozoite VK247 protein for testing vaccine efficacy in a murine model. (December 2016)

• Record Type: Journal Article
• Authors: Mizutani, Masanori; Fukumoto, Shinya; Soubeiga, Adam; Soga, Akira; Iyori, Mitsuhiro; Yoshida, Shigeto
• Is Part Of: Malaria journal. Volume 15:Number 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: Circumsporozoite protein -- Plasmodiumberghei -- Plasmodium vivax -- PvCSP -- Transgenic parasite -- VK210 -- VK247 -- Vaccine; Malaria -- Periodicals; 616.9362
• DOI: 10.1186/s12936-016-1297-3
• Languages: English
• ISSNs: 1475-2875

Abstract

Abstract Background The approach of using transgenic rodent malaria parasites to assess the immune system's response to antigenic targets from a human malaria parasite has been shown to be useful for preclinical evaluation of new vaccine formulations. The transgenicPlasmodium berghei parasite line [PvCSP(VK210)/Pb] generated previously expresses the full-length circumsporozoite protein (CSP) VK210 fromPlasmodium vivax . The transgenic parasite expresses one of the two most common alleles of CSP, defined by nine amino acids at the central repeat region of this protein. In the present study, a transgenicP. berghei parasite line [PvCSP(VK247)/Pb] expressing the full-length PvCSP(VK247), which is the alternative common allele, was generated and characterized. Methods TheP. berghei expressing full-length PvCSP(VK247) was generated and examined its applicability to CSP-based vaccine research by examining its biological characteristics in mosquitoes and mice. Results Similar to PvCSP(VK210)/Pb, PvCSP(VK247)/Pb developed normally in mosquitoes and produced infectious sporozoites equipped to generate patent infections in mice. Invasion of HepG2 cells by PvCSP(VK247)/Pb sporozoites was inhibited by an anti-PvCSP(VK247) repeat monoclonal antibody (mAb), but not by an anti-PvCSP(VK210) repeat mAb. Conclusions These two transgenic parasites thus far can be used to evaluate the potential efficacy of PvCSP-based vaccine candidates encompassing the two major genetic variants in preclinical trials.