Your browser doesn't support javascript.
loading
Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens.
Naung, Myo T; Martin, Elijah; Munro, Jacob; Mehra, Somya; Guy, Andrew J; Laman, Moses; Harrison, G L Abby; Tavul, Livingstone; Hetzel, Manuel; Kwiatkowski, Dominic; Mueller, Ivo; Bahlo, Melanie; Barry, Alyssa E.
Afiliación
  • Naung MT; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Martin E; Department of Medical Biology, University of Melbourne, Carlton, Victoria, Australia.
  • Munro J; Institute of Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Geelong, Victoria, Australia.
  • Mehra S; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Guy AJ; Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia.
  • Laman M; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Harrison GLA; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Tavul L; Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia.
  • Hetzel M; School of Science, RMIT University, Melbourne, Victoria, Australia.
  • Kwiatkowski D; Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
  • Mueller I; Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Bahlo M; Department of Medical Biology, University of Melbourne, Carlton, Victoria, Australia.
  • Barry AE; Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
PLoS Comput Biol ; 18(2): e1009801, 2022 02.
Article en En | MEDLINE | ID: mdl-35108259
Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies of vaccine candidates of the most virulent human malaria parasite, Plasmodium falciparum, have focused on a handful of well-known antigens, while several others have never been studied. Here we examine the global diversity and population structure of leading vaccine candidate antigens of P. falciparum using the MalariaGEN Pf3K (version 5.1) resource, comprising more than 2600 genomes from 15 malaria endemic countries. A stringent variant calling pipeline was used to extract high quality antigen gene 'haplotypes' from the global dataset and a new R-package named VaxPack was used to streamline population genetic analyses. In addition, a newly developed algorithm that enables spatial averaging of selection pressure on 3D protein structures was applied to the dataset. We analysed the genes encoding 23 leading and novel candidate malaria vaccine antigens including csp, trap, eba175, ama1, rh5, and CelTOS. Our analysis shows that current malaria vaccine formulations are based on rare haplotypes and thus may have limited efficacy against natural parasite populations. High levels of diversity with evidence of balancing selection was detected for most of the erythrocytic and pre-erythrocytic antigens. Measures of natural selection were then mapped to 3D protein structures to predict targets of functional antibodies. For some antigens, geographical variation in the intensity and distribution of these signals on the 3D structure suggests adaptation to different human host or mosquito vector populations. This study provides an essential framework for the diversity of P. falciparum antigens to be considered in the design of the next generation of malaria vaccines.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Vacunas contra la Malaria / Antígenos de Protozoos Límite: Animals / Humans Idioma: En Revista: PLoS Comput Biol Asunto de la revista: BIOLOGIA / INFORMATICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Vacunas contra la Malaria / Antígenos de Protozoos Límite: Animals / Humans Idioma: En Revista: PLoS Comput Biol Asunto de la revista: BIOLOGIA / INFORMATICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos