Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening
BackgroundPlasmodium 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 i...
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Frontiers Media S.A.
2024-11-01
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| author | Hojong Jun Ernest Mazigo Ernest Mazigo Wang-Jong Lee Johnsy Mary Louis Jadidan Hada Syahada Fadhila Fitriana Jin Heo Yeonkyung Kim Boeun Kwon Fauzi Muh Feng Lu Md Atique Ahmed Se Jin Lee Sunghun Na Wanjoo Chun Won Sun Park Min Hong Joon-Hee Han Tae-Hyung Kwon Soo-Ung Lee Eun-Teak Han Jim Todd Jim Todd Alphaxard Manjurano Winifrida Kidima Jin-Hee Han |
| author_facet | Hojong Jun Ernest Mazigo Ernest Mazigo Wang-Jong Lee Johnsy Mary Louis Jadidan Hada Syahada Fadhila Fitriana Jin Heo Yeonkyung Kim Boeun Kwon Fauzi Muh Feng Lu Md Atique Ahmed Se Jin Lee Sunghun Na Wanjoo Chun Won Sun Park Min Hong Joon-Hee Han Tae-Hyung Kwon Soo-Ung Lee Eun-Teak Han Jim Todd Jim Todd Alphaxard Manjurano Winifrida Kidima Jin-Hee Han |
| author_sort | Hojong Jun |
| collection | DOAJ |
| description | BackgroundPlasmodium 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.MethodsSamples 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.ResultsThe 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).ConclusionsThese findings underscore the need for future PfRh5-based vaccines to consider for increasing genetic variation and geographical differences in humoral immune responses. |
| format | Article |
| id | doaj-art-cf9a9746deb84b0985a57b4fdd460d06 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-cf9a9746deb84b0985a57b4fdd460d062024-11-18T06:10:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14955131495513Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screeningHojong Jun0Ernest Mazigo1Ernest Mazigo2Wang-Jong Lee3Johnsy Mary Louis4Jadidan Hada Syahada5Fadhila Fitriana6Jin Heo7Yeonkyung Kim8Boeun Kwon9Fauzi Muh10Feng Lu11Md Atique Ahmed12Se Jin Lee13Sunghun Na14Wanjoo Chun15Won Sun Park16Min Hong17Joon-Hee Han18Tae-Hyung Kwon19Soo-Ung Lee20Eun-Teak Han21Jim Todd22Jim Todd23Alphaxard Manjurano24Winifrida Kidima25Jin-Hee Han26Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Parasitic Diseases, National Institute for Medical Research, Dar es Salaam, TanzaniaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaFaculty of Public Health, Department of Epidemiology and Tropical Diseases, Universitas Diponegoro, Semarang, IndonesiaDepartment of Pathogen Biology and Immunology, School of Medicine, Yangzhou University, Yangzhou, ChinaMalaria Division, Indian Council of Medical Research (ICMR)-Regional Medical Research Centre, Dibrugarh, Assam, IndiaDepartment of Obstetrics and Gynecology, Kangwon National University Hospital, Chuncheon, Republic of KoreaDepartment of Obstetrics and Gynecology, Kangwon National University Hospital, Chuncheon, Republic of KoreaDepartment of Pharmacology, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Physiology, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaInstitute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon, Republic of KoreaInstitute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon, Republic of KoreaInstitute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon, Republic of KoreaInstitute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon, Republic of KoreaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea0Department of Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom1Department of Biostatistics, Catholic University of Health and Allied Sciences (CUHAS), Mwanza, TanzaniaDepartment of Parasitic Diseases, National Institute for Medical Research, Dar es Salaam, Tanzania2Department of Zoology, College of Natural and Applied Sciences, University of Dar es Salaam, Dar es Salaam, TanzaniaDepartment of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of KoreaBackgroundPlasmodium 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.MethodsSamples 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.ResultsThe 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).ConclusionsThese findings underscore the need for future PfRh5-based vaccines to consider for increasing genetic variation and geographical differences in humoral immune responses.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1495513/fullmalariaPlasmodium falciparumasymptomaticTanzaniaPfRh5genetic variation |
| spellingShingle | Hojong Jun Ernest Mazigo Ernest Mazigo Wang-Jong Lee Johnsy Mary Louis Jadidan Hada Syahada Fadhila Fitriana Jin Heo Yeonkyung Kim Boeun Kwon Fauzi Muh Feng Lu Md Atique Ahmed Se Jin Lee Sunghun Na Wanjoo Chun Won Sun Park Min Hong Joon-Hee Han Tae-Hyung Kwon Soo-Ung Lee Eun-Teak Han Jim Todd Jim Todd Alphaxard Manjurano Winifrida Kidima Jin-Hee Han Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening Frontiers in Immunology malaria Plasmodium falciparum asymptomatic Tanzania PfRh5 genetic variation |
| title | Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening |
| title_full | Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening |
| title_fullStr | Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening |
| title_full_unstemmed | Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening |
| title_short | Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening |
| title_sort | estimation of pfrh5 based vaccine efficacy in asymptomatic plasmodium falciparum patients from high endemic areas of tanzania using genetic and antigenicity variation screening |
| topic | malaria Plasmodium falciparum asymptomatic Tanzania PfRh5 genetic variation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1495513/full |
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