title: A novel chimeric Plasmodium vivax circumsporozoite protein induces biologically functional antibodies that recognize both VK210 and VK247 sporozoites.
abstract: A successful vaccine against Plasmodium vivax malaria would significantly improve the health and quality of the lives of more than 1 billion people around the world. A subunit vaccine is the only option in the absence of long-term culture of P. vivax parasites. The circumsporozoite protein that covers the surface of Plasmodium sporozoites is one of the best-studied malarial antigens and the most promising vaccine in clinical trials. We report here the development of a novel "immunologically optimal" recombinant vaccine expressed in Escherichia coli that encodes a chimeric CS protein encompassing repeats from the two major alleles, VK210 and VK247. This molecule is widely recognized by sera from patients naturally exposed to P. vivax infection and induces a highly potent immune response in genetically disparate strains of mice. Antibodies from immunized animals recognize both VK210 and VK247 sporozoites. Furthermore, these antibodies appear to be protective in nature since they cause the agglutination of live sporozoites, an in vitro surrogate of sporozoite infectivity. These results strongly suggest that recombinant CS is biologically active and highly immunogenic across major histocompatibility complex strains and raises the prospect that in humans this vaccine may induce protective immune responses.
authors.affiliation: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. anjali.yadava@us.army.mil
authors.forename: Anjali
authors.initials: A
authors.lastname: Yadava
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Michael A
authors.initials: MA
authors.lastname: Washington
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Ware
authors.forename: Victoria
authors.initials: V
authors.lastname: Majam
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Sanjai
authors.initials: S
authors.lastname: Kumar
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology* / Q000378:metabolism; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; C041595:circumsporozoite protein, Protozoan