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. 2012 Feb;19(2):157-66.
doi: 10.1128/CVI.05523-11. Epub 2011 Dec 14.

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

Carlota Dobaño  1 , Diana Quelhas, Llorenç Quintó, Laura Puyol, Elisa Serra-Casas, Alfredo Mayor, Tacilta Nhampossa, Eusebio Macete, Pedro Aide, Inacio Mandomando, Sergi Sanz, Sanjeev K Puniya, Bijender Singh, Puneet Gupta, Arindam Bhattacharya, Virander S Chauhan, John J Aponte, Chetan E Chitnis, Pedro L Alonso, Clara Menéndez
Affiliations

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

Carlota Dobaño et al. Clin Vaccine Immunol. 2012 Feb.

Abstract

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.

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Figures

Fig 1
Fig 1
Antibody responses to asexual blood-stage whole P. falciparum parasites (A), P. falciparum MSP-119 (PfMSP-119) (B), P. falciparum AMA-1 (PfAMA-1) (C), and P. falciparum EBA-175 (PfEBA-175) (D) in children up to 2 years of age. For IFAT data (A), IgG levels (y axes in log scale) are expressed as endpoint titers. For ELISA data (B to D), IgG (left) and IgM (right) levels are expressed as normalized OD values (y axes, percentages). In the weighted scatter plots, the area of the symbol is proportional to the number of observations. Geometric mean IgG titers and 95% confidence intervals are indicated by horizontal continuous and dashed lines, respectively. Red symbols correspond to IgG levels in children with previous or present infection.
Fig 2
Fig 2
IgG subclass responses to MSP-119 (A), AMA-1 (B), and EBA-175 (C) in children up to age 2 years of age. Only data for children receiving IPTi with placebo are depicted here. IgG levels (y axes) are expressed as OD values. In the weighted scatter plots, the area of the symbol is proportional to the number of observations. Geometric mean IgG levels and 95% confidence intervals are indicated by horizontal continuous and dashed lines, respectively.
Fig 3
Fig 3
Map of the Manhiça area with the neighborhoods colored as a function of malaria incidence (number of episodes per PYAR) for children selected for the study during the study period. The map illustrates the geographical microheterogeneity and the significant effect of neighborhood on malaria episodes and antibodies in the multilevel regression models. The study area expands a distance of less than 20 km from north to south and approximately 10 km from east to west and has two study clinics (Manhiça and Maragra). The number of children by groups of neighborhoods is indicated in the table.
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