The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Immunol.
Sec. Parasite Immunology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1495513
This article is part of the Research Topic Dissecting malaria protective immunity: acquired by natural infection and/or vaccination View all 3 articles
Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening
Provisionally accepted- 1 Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea
- 2 Faculty of Public Health, Diponegoro University, Semarang, Central Java, Indonesia
- 3 Department of Pathogen Biology and Immunology, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
- 4 Malaria Division, Indian Council of Medical Research (ICMR), New Delhi, National Capital Territory of Delhi, India
- 5 Department of Obstetrics and Gynecology, Kangwon National University Hospital, Chuncheon, Gangwon, Republic of Korea
- 6 Department of Pharmacology, School of Medicine, Kangwon National University, Chuncheon, Gangwon, Republic of Korea
- 7 Department of Physiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon, Republic of Korea
- 8 Institute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon, Republic of Korea
- 9 Department of Population Health, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, England, United Kingdom
- 10 Department of Parasitic Diseases, National Institute for Medical Research, Dar es Salaam, Tanzania
- 11 College of Natural and Applied Sciences, University of Dar es Salaam, Dar es Salaam, Dar es Salaam, Tanzania
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.
Copyright: © 2024 Han, Jun, Mazigo, Lee, Louis, Syahada, Fitriana, Heo, Kim, Kwon, Muh, Lu, Ahmed, Lee, Na, Chun, Park, Hong, Han, Kwon, Lee, Han, Todd, Manjurano and Kidima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jin-Hee Han, Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.