PREreviews of “Genetic Diversity of the Malaria Vaccine Candidate PfRIPR in a High Transmission Region of Senegal” | PREreview

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Genetic Diversity of the Malaria Vaccine Candidate PfRIPR in a High Transmission Region of Senegal

by Megha Nair, Giselle Geering, Alyssa Agarwal, Rebecca Li, Yujie Qiao, Qin Xiao, Mariama N. Pouye, Laty G. Thiam, Aboubacar Ba, Kelly A. Hagadorn, Awa Cisse, Noemi Guerra, Yome Tawaldemedhen, Khadidiatou Mangou, Adam J. Moore, Fatoumata Diallo, Seynabou D. Sene, Bacary D. Sadio, Elizabeth Zhang, Lawrence Shapiro, Saurabh D. Patel, Alassane Mbengue, Ines Vigan-Womas, Zizhang Sheng, and Amy K. Bei

Posted: September 29, 2025
Server: medRxiv
DOI: 10.1101/2025.09.23.25335263

Abstract

Summary

RH5-Interacting Protein (RIPR) is essential for the invasion of Plasmodium into host red blood cells and is currently being studied as a novel malaria vaccine candidate in Phase 1a clinical trials. To study the genetic diversity of RIPR, deep amplicon sequencing was used to identify RIPR mutations in Plasmodium falciparum clinical isolates (n=89) collected in Kédougou, a high malaria transmission region of Senegal. We identified nonsynonymous single nucleotide polymorphisms (SNPs) in 64/89 (71.9%) of the samples. In total, 26 non-synonymous SNPs were identified, of which 15 were novel. 16/26 SNPs were able to be threaded onto existing RIPR crystal structures to predict the effects of SNPs on RIPR stability. 7/16 mutations were predicted to destabilize RIPR while 2/16 increased the stability of RIPR. Additionally, we identified 3 SNPs (Q737K, T738K, V840L) in the EGF5-8 domains of RIPR where neutralizing antibodies are known to bind.

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3 PREreviews

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PREreview by Irvane Ngnie Kamga

Authored by Irvane Ngnie Kamga

Summary:
This preprint fills a gap in the literature to date by investigating the genetic diversity of RH5-Interacting Protein (PfRIPR) using 89 blood samples from Senegal. This is a highly relevant and timely study given that PfRIPR, which is part of the PTRAMP—CSS—RIPR—CyRPA—RH5 (PCRCR) complex…

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PREreview by Emerald Bee

Authored by Emerald Bee

Summary and Overall Impression:
Overall, this paper presents an in-depth structural analysis of potential SNPs that may cause issues in vaccines targeting the RIPR protein. The authors perform deep amplicon sequencing and successfully identify 15 novel SNPs, in addition to 11 previously described…

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PREreview by Emerald Bee

Authored by Emerald Bee

Summary and Overall Impression:
Overall, this paper presents an in-depth structural analysis of potential SNPs that may cause issues in vaccines targeting the RIPR protein. The authors perform deep amplicon sequencing and successfully identify 15 novel SNPs, in addition to 11 previously described…

Read the PREreview by Emerald Bee