Age-dependent IgG subclass responses to Plasmodium falciparum EBA-175 are differentially associated with incidence of malaria in Mozambican children.

Clin Vaccine Immunol 2012 Feb 14;19(2):157-66. Epub 2011 Dec 14.

Barcelona Centre for International Health Research, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

Plasmodium falciparum blood-stage antigens such as merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and the 175-kDa erythrocyte binding antigen (EBA-175) are considered important targets of naturally acquired immunity to malaria. However, it is not clear whether antibodies to these antigens are effectors in protection against clinical disease or mere markers of exposure. In the context of a randomized, placebo-controlled trial of intermittent preventive treatment in infants conducted between 2002 and 2004, antibody responses to Plasmodium falciparum blood-stage antigens in a cohort of 302 Mozambican children were evaluated by immunofluorescence antibody test and enzyme-linked immunosorbent assay at 5, 9, 12, and 24 months of age. We found that IgG subclass responses to EBA-175 were differentially associated with the incidence of malaria in the follow-up period. A double amount of cytophilic IgG1 or IgG3 was associated with a significant decrease in the incidence of malaria (incidence rate ratio [IRR] = 0.49, 95% confidence interval [CI] = 0.25 to 0.97, and P = 0.026 and IRR = 0.44, CI = 0.19 to 0.98, and P = 0.037, respectively), while a double amount of noncytophilic IgG4 was significantly correlated with an increased incidence of malaria (IRR = 3.07, CI = 1.08 to 8.78, P = 0.020). No significant associations between antibodies to the 19-kDa fragment of MSP-1 (MSP-1(19)) or AMA-1 and incidence of malaria were found. Age, previous episodes of malaria, present infection, and neighborhood of residence were the main factors influencing levels of antibodies to all merozoite antigens. Deeper understanding of the acquisition of antibodies against vaccine target antigens in early infancy is crucial for the rational development and deployment of malaria control tools in this vulnerable population.

Download full-text PDF

Source
http://dx.doi.org/10.1128/CVI.05523-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272921PMC
February 2012
22 Reads

Publication Analysis

Top Keywords

incidence malaria
20
plasmodium falciparum
12
malaria
8
associated incidence
8
eba-175 differentially
8
responses plasmodium
8
mozambican children
8
blood-stage antigens
8
double amount
8
differentially associated
8
igg subclass
8
falciparum blood-stage
8
subclass responses
8
incidence
6
antigens
5
responses eba-175
4
malaria follow-up
4
residence main
4
follow-up period
4
age igg
4

Altmetric Statistics

References

(Supplied by CrossRef)
Manhiça DSS, Mozambique
INDEPTH et al.
2002
Structure of the malaria antigen AMA1 in complex with a growth-inhibitory antibody
Coley et al.
PLoS Pathog. 2007

Similar Publications