Search

Background: 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 high-transmission 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. Methods: Samples for this study were collected from four villages in each of the Kigoma and Geita regions, known malaria transmission hotspots in Tanzania. This community-based cross-sectional study was conducted from December 2022 to July 2023. Genetic variation and natural selection pressure on pfrh5 were analyzed in 164 asymptomatic P. falciparum isolates. The humoral immune response to PfRh5 was also assessed using a protein microarray with 242 sera samples from asymptomatic patients in the same population. Finally, a correlation analysis was conducted to compare pfrh5 genetic variation with the humoral immune response. Results: 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). Conclusions: These findings underscore the need for future PfRh5-based vaccines to consider for increasing genetic variation and geographical differences in humoral immune responses. [ABSTRACT FROM AUTHOR] more...

Babesia bovis , an intraerythrocytic protozoan parasite, causes severe clinical disease in cattle worldwide. The genetic diversity of parasite antigens often results in different immune profiles in infected animals, hindering efforts to develop immune control methodologies against the B . bovis infection. In this study, we analyzed the genetic diversity of the merozoite surface antigen-1 ( msa - 1 ) gene using 162 B . bovis -positive blood DNA samples sourced from cattle populations reared in different geographical regions of Thailand. The identity scores shared among 93 msa - 1 gene sequences isolated by PCR amplification were 43.5–100%, and the similarity values among the translated amino acid sequences were 42.8–100%. Of 23 total clades detected in our phylogenetic analysis, Thai msa - 1 gene sequences occurred in 18 clades; seven among them were composed of sequences exclusively from Thailand. To investigate differential antigenicity of isolated MSA-1 proteins, we expressed and purified eight recombinant MSA-1 (rMSA-1) proteins, including an rMSA-1 from B . bovis Texas (T2Bo) strain and seven rMSA-1 proteins based on the Thai msa - 1 sequences. When these antigens were analyzed in a western blot assay, anti-T2Bo cattle serum strongly reacted with the rMSA-1 from T2Bo, as well as with three other rMSA-1 proteins that shared 54.9–68.4% sequence similarity with T2Bo MSA-1. In contrast, no or weak reactivity was observed for the remaining rMSA-1 proteins, which shared low sequence similarity (35.0–39.7%) with T2Bo MSA-1. While demonstrating the high genetic diversity of the B . bovis msa - 1 gene in Thailand, the present findings suggest that the genetic diversity results in antigenicity variations among the MSA-1 antigens of B . bovis in Thailand. [ABSTRACT FROM AUTHOR] more...