The PfRh5-Basigin ligand–receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype–phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. We found dose-dependent inhibition of invasion across all isolates tested, and no statistically significant difference in invasion inhibition for any single nucleotide polymorphisms. This study demonstrates that PfRh5 remains highly conserved and functionally essential, even in a highly endemic setting, supporting continued development as a strain-transcendent malaria vaccine target.
The recent stall in the global reduction of malaria deaths has made the development of a highly effective vaccine essential. A major challenge to developing an efficacious vaccine is the extensive diversity of Plasmodium falciparum antigens. While genetic diversity plays a major role in immune evasion and is a barrier to the development of both natural and vaccine-induced protective immunity, it has been under-prioritized in the evaluation of malaria vaccine candidates. This study uses genomic approaches to evaluate genetic diversity in next generation malaria vaccine candidate PfRh5. We used targeted deep amplicon sequencing to identify non-synonymous Single Nucleotide Polymorphisms (SNPs) in PfRh5 (Reticulocyte-Binding Protein Homologue 5) in 189 P. falciparum positive samples from Southern Senegal and identified 74 novel SNPs. We evaluated the population prevalence of these SNPs as well as the frequency in individual samples and found that only a single SNP, C203Y, was present at every site. Many SNPs were unique to the individual sampled, with over 90% of SNPs being found in just one infected individual. In addition to population prevalence, we assessed individual level SNP frequencies which revealed that some SNPs were dominant (frequency of greater than 25% in a polygenomic sample) whereas most were rare, present at 2% or less of total reads mapped to the reference at the given position. Structural modeling uncovered 3 novel SNPs occurring under epitopes bound by inhibitory monoclonal antibodies, potentially impacting immune evasion, while other SNPs were predicted to impact PfRh5 structure or interactions with the receptor or binding partners. Our data demonstrate that PfRh5 exhibits greater genetic diversity than previously described, with the caveat that most of the uncovered SNPs are at a low overall frequency in the individual and prevalence in the population. The structural studies reveal that novel SNPs could have functional implications on PfRh5 receptor binding, complex formation, or immune evasion, supporting continued efforts to validate PfRh5 as an effective malaria vaccine target and development of a PfRh5 vaccine.
Vulvovaginal candidiasis (CVV) is a superficial mycosis caused by Candida spp. with a predominance of C. albicans. CVV is opportunistic with several incriminated risk factors. This study aimed to determine the prevalence of CVV and to investigate potential risk factors. A cross-sectional study was carried out at the Medical Biology Laboratory in Pasteur Institute in Dakar, Senegal from September 1 to November 30, 2020. The study cohort was inclusive of all women received for a vaginal swab test in the laboratory unit. Each patient’s socio-demographic and clinical data were recorded before collecting two swabs samples for direct examination and culture on CHROMagar Candida incubated at 37 °C for 24 to 48 h. A total of 312 women with an average age of 32 years (range: 17-74) were included in this study. An overall CVV prevalence of 32% was found. C. albicans was predominant (73.2%) followed by C. glabrata (16.8%). The age group [30-40 years] was more infested with 35.3% (p = 0.434) as well as nulliparous or primiparous women with 38.7% (p = 0.171). CVV was more associated with disordered vaginal flora and pregnancy with 35.2% (p = 0.323) and 33.7% (p = 0.715) respectively. CVV was significantly related to contraception (p = 0.014). An overall high prevalence of CVV was observed mainly due to C. albicans. Contraception seems to be a factor contributing to its occurrence.
The emergence of artemisinin partial resistance (ART-r) in Plasmodium falciparum malaria parasites has substantially compromised the efficacy of antimalarial treatments across southeast Asia (SE Asia). The spread of ART-r within the African continent could jeopardize past progress made in reducing worldwide malaria burden. A clinical index malaria case was identified in Kaolack, Senegal with persistent fever after complete artesunate-amodiaquine (ASAQ) treatment. Fifteen malaria-infected blood samples were collected by Institut Pasteur Dakar’s Senegalese sentinel surveillance system, from different healthcare centers surrounding the index case. We have identified one Plasmodium falciparum clinical isolate carrying R515K mutation in the artemisinin resistance gene PfKelch13. CRISPR-Cas9 genome editing was carried out and transgenic Pf3D7Pfkelch13R515K was tested for in vitro standard Ring-stage Survival Assay (RSA0-3hpi). Gene editing has confirmed that PfKelch13R515K drove increased in vitro RSA0-3hpi value. In this article, we report the functional significance of PfKelch13R515K mutation in an African context.
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