Differing rates of antibody acquisition to merozoite antigens in malaria: implications for immunity and surveillance.
Antibodies play a key role in acquired human immunity toPlasmodium falciparum(Pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity. We examined responses to a range of merozoite antigens in 2 different cohorts of children and adults with different age structures and levels of malaria exposure. Overall, antibodies were associated with age, exposure, and active infection, and the repertoire of responses increased with age and active infection. However, rates of antibody acquisition varied between antigens and different regions within an antigen following exposure to malaria, supporting our hypothesis. Antigen-specific responses could be broadly classified into early response types in which antibodies were acquired early in childhood exposure and late response types that appear to require substantially more exposure for the development of substantial levels. We identified antigen-specific responses that were effectively boosted after recent infection, whereas other responses were not. These findings advance our understanding of the acquisition of human immunity to malaria and are relevant to the development of malaria vaccines targeting merozoite antigens and the selection of antigens for use in malaria surveillance.
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.|Department of Drug Evaluation, Australian Army Malaria Institute, Brisbane, Australia.
Fiona J
FJ
McCallum
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.|Department of Laboratory Medicine, Lund University, Lund, Sweden.
Kristina E M
KE
Persson
Burnet Institute for Medical Research and Public Health, Melbourne, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia.|Departments of Epidemiology and Preventive Medicine and Infectious Diseases, Monash University, Melbourne, Australia.
Freya J I
FJ
Fowkes
Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
Linda
L
Reiling
Burnet Institute for Medical Research and Public Health, Melbourne, Australia.|Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.
Cleopatra K
CK
Mugyenyi
Burnet Institute for Medical Research and Public Health, Melbourne, Australia.|Department of Microbiology, Monash University, Melbourne, Australia.|Department of Medicine, University of Melbourne, Parkville, Australia.
Jack S
JS
Richards
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia.
Julie A
JA
Simpson
Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.|Department of Medicine, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Thomas N
TN
Williams
Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
Paul R
PR
Gilson
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
Anthony N
AN
Hodder
Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
Paul R
PR
Sanders
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, Latrobe University, Melbourne, Australia.
Robin F
RF
Anders
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
David L
DL
Narum
Institute Pasteur, Paris, France; and.
Chetan
C
Chitnis
Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
Brendan S
BS
Crabb
Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya.|Nuffield Department of Medicine, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, United Kingdom.
Kevin
K
Marsh
Burnet Institute for Medical Research and Public Health, Melbourne, Australia; beeson@burnet.edu.au.|Department of Microbiology, Monash University, Melbourne, Australia.|Department of Medicine, University of Melbourne, Parkville, Australia.
James G
JG
Beeson
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000913:Antibodies, Protozoan / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007109:Immunity; D007074:Immunoglobulin G / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D052940:Merozoites / Q000276:immunology*; D008875:Middle Aged; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G
P. falciparum; children; serosurveillance; vaccines