Format

Send to

Choose Destination
Malar J. 2018 Apr 25;17(1):178. doi: 10.1186/s12936-018-2323-4.

Convalescent Plasmodium falciparum-specific seroreactivity does not correlate with paediatric malaria severity or Plasmodium antigen exposure.

Author information

1
Albert Einstein College of Medicine, Bronx, NY, USA.
2
Antigen Discovery Inc, Irvine, CA, USA.
3
Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
4
College of Medicine, Biomedical Department, University of Malawi, Blantyre, Malawi.
5
Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi.
6
The University of Melbourne, Melbourne, Australia.
7
College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA. seydel@msu.edu.
8
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi. seydel@msu.edu.
9
Albert Einstein College of Medicine, Bronx, NY, USA. kamikim.usf@gmail.com.
10
Morsani College of Medicine, University of South Florida, Tampa, FL, USA. kamikim.usf@gmail.com.

Abstract

BACKGROUND:

Antibody immunity is thought to be essential to prevent severe Plasmodium falciparum infection, but the exact correlates of protection are unknown. Over time, children in endemic areas acquire non-sterile immunity to malaria that correlates with development of antibodies to merozoite invasion proteins and parasite proteins expressed on the surface of infected erythrocytes.

RESULTS:

A 1000 feature P. falciparum 3D7 protein microarray was used to compare P. falciparum-specific seroreactivity during acute infection and 30 days after infection in 23 children with uncomplicated malaria (UM) and 25 children with retinopathy-positive cerebral malaria (CM). All children had broad P. falciparum antibody reactivity during acute disease. IgM reactivity decreased and IgG reactivity increased in convalescence. Antibody reactivity to CIDR domains of "virulent" PfEMP1 proteins was low with robust reactivity to the highly conserved, intracellular ATS domain of PfEMP1 in both groups. Although children with UM and CM differed markedly in parasite burden and PfEMP1 exposure during acute disease, neither acute nor convalescent PfEMP1 seroreactivity differed between groups. Greater seroprevalence to a conserved Group A-associated ICAM binding extracellular domain was observed relative to linked extracellular CIDRα1 domains in both case groups. Pooled immune IgG from Malawian adults revealed greater reactivity to PfEMP1 than observed in children.

CONCLUSIONS:

Children with uncomplicated and cerebral malaria have similar breadth and magnitude of P. falciparum antibody reactivity. The utility of protein microarrays to measure serological recognition of polymorphic PfEMP1 antigens needs to be studied further, but the study findings support the hypothesis that conserved domains of PfEMP1 are more prominent targets of cross reactive antibodies than variable domains in children with symptomatic malaria. Protein microarrays represent an additional tool to identify cross-reactive Plasmodium antigens including PfEMP1 domains that can be investigated as strain-transcendent vaccine candidates.

KEYWORDS:

Antibody; Cerebral malaria; PfEMP1; Plasmodium falciparum; Protein microarray; Uncomplicated malaria

PMID:
29695240
PMCID:
PMC5918990
DOI:
10.1186/s12936-018-2323-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center