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

Abhai K. Tripathi, Miranda S. Oakley, Nitin Verma, Godfree Mlambo, Hong Zheng, Scott M. Meredith, Edward Essuman, Ankit Puri, Richard A. Skelton, Kazuyo Takeda, Victoria Majam, Isabella A. Quakyi, Emily Locke, Merribeth Morin, Kazutoyo Miura, Carole A. Long, Sanjai Kumar

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbereabg2112
JournalScience translational medicine
Volume13
Issue number597
DOIs
StatePublished - Jun 9 2021

ASJC Scopus subject areas

  • General Medicine

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