title: Strain-transcending immune response generated by chimeras of the malaria vaccine candidate merozoite surface protein 2.
abstract: MSP2 is an intrinsically disordered protein that is abundant on the merozoite surface and essential to the parasite Plasmodium falciparum. Naturally-acquired antibody responses to MSP2 are biased towards dimorphic sequences within the central variable region of MSP2 and have been linked to naturally-acquired protection from malaria. In a phase IIb study, an MSP2-containing vaccine induced an immune response that reduced parasitemias in a strain-specific manner. A subsequent phase I study of a vaccine that contained both dimorphic forms of MSP2 induced antibodies that exhibited functional activity in vitro. We have assessed the contribution of the conserved and variable regions of MSP2 to the generation of a strain-transcending antibody response by generating MSP2 chimeras that included conserved and variable regions of the 3D7 and FC27 alleles. Robust anti-MSP2 antibody responses targeting both conserved and variable regions were generated in mice, although the fine specificity and the balance of responses to these regions differed amongst the constructs tested. We observed significant differences in antibody subclass distribution in the responses to these chimeras. Our results suggest that chimeric MSP2 antigens can elicit a broad immune response suitable for protection against different strains of P. falciparum.
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia.
authors: Bankala
authors: B
authors: Krishnarjuna
authors: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia.
authors: Dean
authors: D
authors: Andrew
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia.
authors: Christopher A
authors: CA
authors: MacRaild
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia.
authors: Rodrigo A V
authors: RA
authors: Morales
authors: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia.|Department of Microbiology, Monash University, Clayton 3800, Australia.|Department of Medicine, University of Melbourne, Parkville 3052, Australia.
authors: James G
authors: JG
authors: Beeson
authors: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors: Robin F
authors: RF
authors: Anders
authors: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia.|Department of Microbiology, Monash University, Clayton 3800, Australia.|Department of Medicine, University of Melbourne, Parkville 3052, Australia.
authors: Jack S
authors: JS
authors: Richards
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia.
authors: Raymond S
authors: RS
authors: Norton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000097:blood / Q000145:classification; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002986:Clinical Trials as Topic; D017124:Conserved Sequence; D056738:Cross Protection; D018604:Epitope Mapping; D000939:Epitopes; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D000071497:Immunogenicity, Vaccine; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000145:classification; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D052940:Merozoites / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum / Q000737:chemistry / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C065974:merozoite surface protein 2, Plasmodium