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

Malaria vaccines that disrupt the 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 antigens that indisputably and reproducibly demonstrate transmission-blocking immunity. So...

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Bibliographic Details
Published in:Science translational medicine 2021-06, Vol.13 (597), p.1
Main Authors: Tripathi, Abhai K, Oakley, Miranda S, Verma, Nitin, Mlambo, Godfree, Zheng, Hong, Meredith, Scott M, Essuman, Edward, Puri, Ankit, Skelton, Richard A, Takeda, Kazuyo, Majam, Victoria, Quakyi, Isabella A, Locke, Emily, Morin, Merribeth, Miura, Kazutoyo, Long, Carole A, Kumar, Sanjai
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Language:English
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Summary:Malaria vaccines that disrupt the 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 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 TBV antigens that, upon immunization, induced antibodies that caused reductions in oocyst counts in 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.
ISSN:1946-6234
1946-6242
1946-3242
DOI:10.1126/scitranslmed.abg2112