The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria.
Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity.
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.|Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
Rupert
R
Weaver
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
Linda
L
Reiling
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
Gaoqian
G
Feng
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
Damien R
DR
Drew
Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.|ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clinic, University of Barcelona, Barcelona, Spain.
Ivo
I
Mueller
Papua New Guinea Institute for Medical Research, Goroka, Papua New Guinea.
Peter M
PM
Siba
Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
Takafumi
T
Tsuboi
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.|Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.|Department of Microbiology and Central Clinical School, Monash University, Melbourne, Australia.
Jack S
JS
Richards
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Australia.|Department of Epidemiology and Preventive Medicine and Department of Infectious Diseases, Monash University, Melbourne, Australia.
Freya J I
FJI
Fowkes
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.|Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.|Department of Microbiology and Central Clinical School, Monash University, Melbourne, Australia.
James G
JG
Beeson
D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000145:classification*; D008137:Longitudinal Studies; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D010219:Papua New Guinea; D018512:Parasitemia / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000276:immunology*; D012307:Risk Factors
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C531020:RH5 protein, Plasmodium falciparum; C000622046:Ripr protein, Plasmodium falciparum