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J Infect Dis. 2019 Nov 6;220(12):1950-1961. doi: 10.1093/infdis/jiz407.

Induction and Kinetics of Complement-Fixing Antibodies Against Plasmodium vivax Merozoite Surface Protein 3α and Relationship With Immunoglobulin G Subclasses and Immunoglobulin M.

Oyong DA1,2, Wilson DW3,4, Barber BE1,5,6, William T5,7, Jiang J8, Galinski MR8,9, Fowkes FJI4,10,11,12,13, Grigg MJ1,5, Beeson JG4,14,15, Anstey NM1,5, Boyle MJ1,4,6.

Author information

1
Menzies School of Health Research, Darwin, Australia.
2
Charles Darwin University, Darwin, Australia.
3
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Melbourne, Australia.
4
Burnet Institute, Melbourne, Australia.
5
Infectious Diseases Society Kota Kinabalu, Sabah-Menzies School of Health Research Clinical Research Unit, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia.
6
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
7
Gleneagles Medical Centre, Kota Kinabalu, Malaysia.
8
Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, Georgia.
9
Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia.
10
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
11
Department of Infectious Diseases, Monash University, Melbourne, Australia.
12
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
13
Department of Immunology and Pathology, Monash University, Melbourne, Australia.
14
Department of Microbiology, Monash University, Clayton, Australia.
15
Department of Medicine, University of Melbourne, Parkville, Australia.

Abstract

BACKGROUND:

Complement-fixing antibodies are important mediators of protection against Plasmodium falciparum malaria. However, complement-fixing antibodies remain uncharacterized for Plasmodium vivax malaria. P. vivax merozoite surface protein 3α (PvMSP3α) is a target of acquired immunity and a potential vaccine candidate.

METHODS:

Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Complement-fixing antibodies and immunoglobulin M and G (IgM and IgG), targeting 3 distinctive regions of PvMSP3α, were measured by means of enzyme-linked immunosorbent assay.

RESULTS:

The seroprevalence of complement-fixing antibodies was highest against the PvMSP3α central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q fixation, and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3α. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Levels of functional antibodies increased after acute infection through 7 days after treatment but rapidly waned by day 28.

CONCLUSION:

Our study demonstrates that PvMSP3α antibodies acquired during P. vivax infection can mediate complement fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.

KEYWORDS:

Plasmodium vivax ; Complement-fixing antibodies; PvMSP3α; malaria

PMID:
31419296
PMCID:
PMC6834073
[Available on 2020-11-06]
DOI:
10.1093/infdis/jiz407

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