Sané Rokhaya, Sambe Babacar Souleymane, Diagne Aissatou, Faye Joseph, Sarr Fatoumata Diene, Diaw Serigne Ousmane Mbacké, Sarr Ibrahima, Diatta Arona Sabène, Diatta Hélène Ataume Mawounge, Sembène Papa Mbacké, Vigan-Womas Inès, Toure-Balde Aissatou, Osier Faith, Niang Makhtar
Pôle Immunophysiopathologie et Maladies Infectieuses, Institut Pasteur de Dakar, 36 Avenue Pasteur, 220, Dakar, Senegal.
Département de Biologie Animale, Faculté des Sciences et Techniques, Université Cheikh Anta Diop de Dakar, Dakar, Fann, Sénégal.
Sci Rep. 2025 May 13;15(1):16516. doi: 10.1038/s41598-025-00784-y.
The merozoite surface antigen Pf41 was previously identified among the top 10 of new malaria vaccine candidates. Pf41 possesses red blood cell binding regions and conserved domains. We used population genetics approaches to determine the genetic diversity and to identify regions under balancing selection for the potential inclusion of Pf41 as candidate in a multicomponent vaccine. We screened 116 clinical isolates collected from different administrative regions in Senegal for P. falciparum positivity, Pf41 amplification and sequencing. We analyzed Pf41 sequences for polymorphism, natural selection, haplotype prevalence and linkage disequilibrium. Neutrality tests (Tajima's D, FLD, FLF and MEME) were computed using DnaSP v6. and Datamonkey Hyphy. Population Analysis with Reticulate Trees (Popart) version 1.7 software was used to construct haplotypes network showing the distribution of haplotypes per study site. P. falciparum positivity from the 116 successfully tested samples was 93.1% of which 73 were successfully sequenced for Pf41. We found a low genetic diversity (π = 0.00144 ± 0.00022) and high haplotype diversity (Hd = 0.765 ± 0.037) of Pf41 sequences that can be attributed to linkage disequilibrium. We identified several substitutions under positive selection and negatively selected codons at inter-species level in the central and 6-Cys domains of Pf41, respectively. The predominant SNP S232R was found fixed by positive selection in Senegalese isolates. The genetic diversity of Pf41 antigen is low in clinical isolates from Senegal. With a central domain under balancing selection and two highly conserved 6-Cys domains under negative selection due to functional constraints, the Pf41 antigen appears as a good vaccine candidate. Further monitoring of allelic variants on larger and diverse sets of samples would justify the rational for functional assays and Pf41 integration in a multicomponent vaccine.
裂殖子表面抗原Pf41先前被确定为新型疟疾疫苗候选物中的前10名。Pf41具有红细胞结合区域和保守结构域。我们使用群体遗传学方法来确定遗传多样性，并识别处于平衡选择下的区域，以便将Pf41作为候选物纳入多组分疫苗。我们筛选了从塞内加尔不同行政区收集的116份临床分离株，检测恶性疟原虫阳性、Pf41扩增和测序情况。我们分析了Pf41序列的多态性、自然选择、单倍型流行率和连锁不平衡。使用DnaSP v6和Datamonkey Hyphy计算中性检验（ Tajima's D、FLD、FLF和MEME）。使用网状树群体分析（Popart）1.7版软件构建单倍型网络，显示每个研究地点单倍型的分布。116份成功检测的样本中恶性疟原虫阳性率为93.1%，其中73份成功进行了Pf41测序。我们发现Pf41序列的遗传多样性较低（π = 0.00144 ± 0.00022），单倍型多样性较高（Hd = 0.765 ± 0.037），这可归因于连锁不平衡。我们在Pf41的中央结构域和6-半胱氨酸结构域的种间水平分别鉴定出了几个正选择下的替换和负选择密码子。在塞内加尔分离株中，主要的SNP S232R通过正选择被固定下来。来自塞内加尔的临床分离株中Pf41抗原遗传多样性较低。由于功能限制，Pf41抗原的中央结构域处于平衡选择之下，两个高度保守的6-半胱氨酸结构域处于负选择之下，它似乎是一个很好的疫苗候选物。对更大且多样的样本集上的等位基因变体进行进一步监测，将为功能测定和Pf41纳入多组分疫苗的合理性提供依据。
