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

doi:10.1126/scitranslmed.abg2112

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

Sci Transl Med. 2021 Jun 9;13(597):eabg2112. doi: 10.1126/scitranslmed.abg2112.

Authors

Abhai K Tripathi¹, Miranda S Oakley², Nitin Verma², Godfree Mlambo¹, Hong Zheng², Scott M Meredith², Edward Essuman², Ankit Puri², Richard A Skelton², Kazuyo Takeda³, Victoria Majam², Isabella A Quakyi⁴, Emily Locke⁵, Merribeth Morin⁵, Kazutoyo Miura⁶, Carole A Long⁶, Sanjai Kumar⁷

Affiliations

¹ Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
² Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
³ Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
⁴ School of Public Health, University of Ghana, Accra, Ghana.
⁵ PATH-Malaria Vaccine Initiative, Washington, DC 20001, USA.
⁶ Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
⁷ Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA. sanjai.kumar@fda.hhs.gov.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Antibodies, Protozoan
Antigens, Protozoan / genetics
Ghana
Malaria Vaccines*
Malaria, Falciparum* / prevention & control
Male
Plasmodium falciparum

Substances

Antibodies, Protozoan
Antigens, Protozoan
Malaria Vaccines

Grants and funding

Z99 AI999999/ImNIH/Intramural NIH HHS/United States