Research ArticleMalaria

Plasmodium falciparum Pf77 and male development gene 1 as vaccine antigens that induce potent transmission-reducing antibodies

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Science Translational Medicine  09 Jun 2021:
Vol. 13, Issue 597, eabg2112
DOI: 10.1126/scitranslmed.abg2112

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Additional antigens for malaria

Despite extensive research, malaria vaccines that disrupt the Plasmodium life cycle and prevent transmission are lacking. Thus, there is a critical need for new targets for transmission-blocking vaccines (TBVs). Here, Tripathi et al. identified Pf77 and male development gene 1 (PfMDV-1) from Plasmodium falciparum that are expressed at multiple life stages and induce transmission-reducing antibodies when administered to mice. Antibodies targeting Pf77 and PfMDV-1 were also identified in a cohort of adults in Ghana, suggesting that targeting these antigens may induce durable immune responses in humans. Together, Pf77 and PfMDV-1 merit further evaluation as TBV candidates.

Abstract

Malaria vaccines that disrupt the Plasmodium life cycle in mosquitoes and reduce parasite transmission in endemic areas are termed transmission-blocking vaccines (TBVs). Despite decades of research, there are only a few Plasmodium falciparum antigens that indisputably and reproducibly demonstrate transmission-blocking immunity. So far, only two TBV candidates have advanced to phase 1/2 clinical testing with limited success. By applying an unbiased transcriptomics-based approach, we have identified Pf77 and male development gene 1 (PfMDV-1) as two P. falciparum TBV antigens that, upon immunization, induced antibodies that caused reductions in oocyst counts in Anopheles mosquito midguts in a standard membrane feeding assay. In-depth studies were performed to characterize the genetic diversity of, stage-specific expression by, and natural immunity to these two molecules to evaluate their suitability as TBV candidates. Pf77 and PfMDV-1 display limited antigenic polymorphism, are pan-developmentally expressed within the parasite, and induce naturally occurring antibodies in Ghanaian adults, which raises the prospect of natural boosting of vaccine-induced immune response in endemic regions. Together, these biological properties suggest that Pf77 and PfMDV-1 may warrant further investigation as TBV candidates.

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