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

Masanori Mizutani,Mitsuhiro Iyori,Akira Soga,Shinya Fukumoto,Adam Patrice Soubeiga,Shigeto Yoshida

doi:10.1186/s12936-016-1297-3

Masanori Mizutani, Mitsuhiro Iyori + Show 4 more

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https://doi.org/10.1186/s12936-016-1297-3

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Abstract

BackgroundThe 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 transgenic Plasmodium berghei parasite line [PvCSP(VK210)/Pb] generated previously expresses the full-length circumsporozoite protein (CSP) VK210 from Plasmodium 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 transgenic P. berghei parasite line [PvCSP(VK247)/Pb] expressing the full-length PvCSP(VK247), which is the alternative common allele, was generated and characterized.MethodsThe P. 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.ResultsSimilar 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.ConclusionsThese 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.

Highlights

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
One complication impeding the development of a P. vivax vaccine is that, in contrast to Plasmodium falciparum, there are two common PvCSP alleles; these alleles consist of nine amino acids at the central repeat regions, GDRA[D/A]GQPA and ANGAGNQPG, thereby defining the sequence variants known as VK210 and VK247, respectively [9, 10]
PvCSP(VK247)/Pb sporozoites reacted strongly with an anti-PvCSP(VK247) monoclonal antibody (mAb) specific for the repeat region, and sporozoite invasion of HepG2 cells by PvCSP(VK247)/Pb was inhibited by the same mAb. These results suggest that these two transgenic parasites can be used to evaluate the potential efficacy of the two PvCSP-based vaccine candidates encompassing the two major genetic variants, making clinical trials of the two alternative forms of the CSPbased vaccine possible using a murine model of P. vivax infection

Summary

Introduction

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 transgenic Plasmodium berghei parasite line [PvCSP(VK210)/Pb] generated previously expresses the full-length circumsporozoite protein (CSP) VK210 from Plasmodium 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. One complication impeding the development of a P. vivax vaccine is that, in contrast to Plasmodium falciparum, there are two common PvCSP alleles; these alleles consist of nine amino acids at the central repeat regions, GDRA[D/A]GQPA and ANGAGNQPG, thereby defining the sequence variants known as VK210 and VK247, respectively [9, 10]. A transgenic P. berghei parasite expressing the full-length PvCSP(VK210) allele [PvCSP(VK210)/Pb] has been developed and showed that the newly developed PvCSP vaccine elicited protective efficacy against infection with this transgenic parasite line [18]

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