Jun Hojong, Mazigo Ernest, Lee Wang-Jong, Louis Johnsy Mary, Syahada Jadidan Hada, Fitriana Fadhila, Heo Jin, Kim Yeonkyung, Kwon Boeun, Muh Fauzi, Lu Feng, Ahmed Md Atique, Lee Se Jin, Na Sunghun, Chun Wanjoo, Park Won Sun, Hong Min, Han Joon-Hee, Kwon Tae-Hyung, Lee Soo-Ung, Han Eun-Teak, Todd Jim, Manjurano Alphaxard, Kidima Winifrida, Han Jin-Hee
Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
Department of Parasitic Diseases, National Institute for Medical Research, Dar es Salaam, Tanzania.
Front Immunol. 2024 Nov 18;15:1495513. doi: 10.3389/fimmu.2024.1495513. eCollection 2024.
is the most lethal malaria parasite. Recent phase 1b vaccine trials using 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.
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 were analyzed in 164 asymptomatic 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.
The results revealed that 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 ( = 0.170, = 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.
疟原虫是最致命的疟原虫。最近使用网织红细胞结合蛋白同源物5（PfRh5）进行的1b期疫苗试验证明了其在预防裂殖子入侵方面的安全性和有前景的疗效。由于PfRh5在裂殖子入侵中起关键作用且序列变异有限，它已成为强有力的疫苗候选物。对于有效的疟疾疫苗开发，特别是在高传播环境中，必须考虑菌株超越活性。持续监测抗原变异和自然免疫反应对于评估不同地理区域人群的疫苗效力很重要。
本研究的样本来自坦桑尼亚已知的疟疾传播热点地区基戈马和吉塔地区的每个四个村庄。这项基于社区的横断面研究于2022年12月至2023年7月进行。对164株无症状疟原虫分离株分析了疟原虫的遗传变异和自然选择压力。还使用蛋白质微阵列对来自同一人群无症状患者的242份血清样本评估了对PfRh5的体液免疫反应。最后，进行相关性分析以比较pfrh5基因变异与体液免疫反应。
结果显示疟原虫高度保守，但在D65H、H170N和I227M处发现了新的非同义突变。此外，自然选择指标表明研究区域内PfRh5存在正选择潜力和近期种群扩张，这两者都可能影响疫苗效力。抗原性筛查显示敏感性各不相同，从布尼扬博的3.3%到卢旺达塔巴的82.8%，抗原性与寄生虫血症、单倍型或性别之间无显著关系。然而，年龄与体液免疫反应显著相关（ = 0.170， = 0.008）。
这些发现强调了未来基于PfRh5的疫苗需要考虑增加基因变异和体液免疫反应中的地理差异。
