| Autor: |
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 |
| Předmět: |
|
| Zdroj: |
Science Translational Medicine; 6/9/2021, Vol. 13 Issue 597, p1-11, 11p |
| Abstrakt: |
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. 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
