Front. Immunol.

Sec. Parasite Immunology

Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1495513

Provisionally accepted

The final, formatted version of the article will be published soon.

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Plasmodium falciparum is the most lethal malaria parasite. Recent phase 1b vaccine trials using P. falciparum reticulocyte binding protein homolog 5 (PfRh5) demonstrated safety and promising efficacy in preventing merozoite invasion. PfRh5 has emerged as a strong vaccine candidate due to its essential role in merozoite invasion and limited sequence variation. For effective malaria vaccine development, especially in hightransmission settings, strain-transcending activity must be considered. Ongoing monitoring of antigenic variation and natural immune responses is important to estimate vaccine efficacy across geographically diverse populations.This study analyzed the genetic variation of pfrh5 in 164 asymptomatic P. falciparum clinical isolates from high malaria transmission villages in Geita and Kimoga regions of Tanzania. The results revealed that pfrh5 was well conserved, but novel non-synonymous mutations were found at D65H, H170N, and I227M. Additionally, natural selection metrics indicated the potential for positive selection and a recent population expansion of PfRh5 in the study area, both of which could influence vaccine effectiveness. Antigenicity screening revealed variable sensitivity, ranging from 3.3% in Bunyambo to 82.8% in Rwantaba, with no significant relationship between antigenicity and parasitemia, haplotypes, or gender. However, age was significantly associated with humoral immune response (ρ = 0.170, p = 0.008). These findings underscore the need for future PfRh5-based vaccines to consider for increasing genetic variation and geographical differences in humoral immune responses.

Keywords: Malaria, Plasmodium falciparum, asymptomatic, Tanzania, PfRh5, Genetic Variation, Antigenicity variation, Vaccine

Received: 12 Sep 2024; Accepted: 29 Oct 2024.

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