Genetic diversity of the malaria vaccine candidate PfRIPR in a high transmission region of Senegal
RH5-interacting protein (RIPR) is essential for the invasion of <i>Plasmodium</i> 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 <i>Plasmodium falciparum</i> clinical isolates (<i>n</i> = 89) collected in Kédougou, a high malaria transmission region of Senegal. We identified non-synonymous single-nucleotide polymorphisms (SNPs) in 64/89 (71.9%) of samples. In total, 26 non-synonymous SNPs were identified, including 15 novel SNPs. Sixteen of 26 SNPs could be threaded onto existing PfRIPR crystal structures to predict the effects of SNPs on RIPR stability. Seven of 16 mutations were predicted to destabilize PfRIPR, while two of 16 were predicted to increase the stability of RIPR. Additionally, we identified 3 SNPs (Q737K, T738K, and V840L) in the EGF5-8 domains of PfRIPR where neutralizing antibodies are known to bind.
Authors
- Rebecca Li (ORCID: https://orcid.org/0000-0002-2095-7550)
- Seynabou D. Sene (ORCID: https://orcid.org/0000-0003-2812-0680)
- Alassane Mbengue (ORCID: https://orcid.org/0000-0002-4210-6167)
- Aboubacar Ba (ORCID: https://orcid.org/0000-0003-2351-2394)
- Kelly A. Hagadorn (ORCID: https://orcid.org/0000-0001-7200-7023)
- Laty Gaye Thiam (ORCID: https://orcid.org/0000-0001-7086-4726)
- Mariama N. Pouye (ORCID: https://orcid.org/0000-0001-9067-2713)
- Bacary Djilocalisse Sadio
- Alyssa Agarwal (ORCID: https://orcid.org/0000-0001-7276-1034)
- Gayla Geering
- Saurabh D. Patel (ORCID: https://orcid.org/0000-0002-5738-3175)
- Elizabeth Zhang (ORCID: https://orcid.org/0000-0002-1117-8635)
- Khadidiatou Mangou (ORCID: https://orcid.org/0000-0002-0356-0228)
- Noemi Guerra (ORCID: https://orcid.org/0009-0008-8472-7130)
- Adam J. Moore (ORCID: https://orcid.org/0000-0001-8961-1737)
- Yome Tawaldemedhen
- Megha A Nair
- Zizhang Sheng
- Awa Cisse
- Lawrence Shapiro
- Fatoumata Diallo
- Yujie Qiao
- Amy K. Bei
- Ines Vigan-Womas
- Qin Xiao
Institutions
- Aaron Diamond AIDS Research Center (US)
- Yale University (US)
- Institut Pasteur de Dakar (SN)
- Columbia University (US)
Publication Details
- Journal
- iScience
- Published
- 2026-02-03
- DOI
- https://doi.org/10.1016/j.isci.2026.114883
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 0.00