Antibody response to full-length VAR2CSA in children from Ngali II and Ntouessong villages in the center region of Cameroon.

Belanquale Claude Asaba
Microbiology, Parasitology, Hematology and infectious diseases, University of Yaounde 1
June, 2018


Pregnant women are more susceptible to malaria than their non-pregnant counterparts. When P. falciparum infect pregnant women, it evades splenic clearance, by sequestrating in the placenta, causing placental malaria which has several adverse outcomes to both the mother and her foetus. P. falciparum infected Red blood cells in pregnant women, express an antigen called VAR2CSA, which is known as the unique var gene, that mediates binding of infected Red Blood cells (IRBC) to Chondroitin Sulphate A(CSA) at the level of the placenta syncytiotrophoblast. Pregnant women exposed to malaria produce antibodies to VAR2CSA and high levels of antibodies to VAR2CSA are associated with better pregnancy outcomes. This suggests that immunity to VAR2CSA could be protective against placental malaria. The VAR2CSA based vaccine, is the main candidate vaccine to prevent placental malaria. Studies have shown that antibodies to VAR2CSA are present in children. Acquired from their mother or which they produce later in life. If a VAR2CSA vaccine is to be given in children, when antibody levels are high, it may be neutralized. The exact time when maternally transferred antibodies to VAR2CSA markedly decline in infants, and the magnitude of antibody response to VAR2CSA in children later in life, is not clearly known.
Our general objective was to evaluate the antibody response to full-length VAR2CSA in children from Ngali II and Ntouessong villages in the center region of Cameroon. Specifically 1) To determine when maternal IgG to full-length VAR2CSA markedly decline in neonates. 2) To determine the magnitude of antibody response to full-length VAR2CSA in children aged 2-15 years. 3) To determine the influence of maternal placental malaria status and parity on the antibody levels to full-length VAR2CSA in neonates.
Our study was designed as part of a cohort study in Cameroonian children earlier enrolled in a previous study, investigating the influence of Intermittent Preventive Treatment (IPT) with Sulfadoxine Pyrimithemine (SP) on malaria in pregnancy (IPT study) between 2008 and 2013. Another group of children aged 2-15 years, enrolled in 2017. Some pregnant women were diagnosed with malaria and placental malaria confirmed by microscopy of peripheral blood and placental impression smears and histology respectively. Neonates of these women were screened for malaria during monthly visits, using thin and thick films. The MagPix Multiplex Analyte Platform (MAP) assay by the Luminex® Corporation was used to measure antibody levels to the P.f. antigens FCR3 FV2 and FV2 3D7.
In this study, were 49 neonates with monthly visits from birth till one year. And 30 children aged 2-15 years. Antibody levels to full-length VAR2CSA, declined successively from birth till 5 months. There was a significant difference in antibody levels between visits (P<0.0001).
The thirty children, were divided into two age groups. Children less than or 5 years and those greater than 5 years. The magnitude of antibody response was weak with only 1 out of the 30 children (3%) expressing antibodies to VAR2CSA.
Forty-nine mothers of the neonates were included in this study. Twelve were primigravidae and 37 multigravidae. Twenty-five (51%) were diagnosed with pregnancy associated malaria with 6 (12%) of them diagnosed with placental malaria. Primigravidae were significantly most affected with PAM and placental malaria (P<0.0001). Antibody levels were non significantly higher in neonates of mothers who were positive for pregnancy associated malaria compared to those of neonates, whose mothers did not have malaria. Neonates of multigravidae, had non significantly higher antibody levels compared to those of primigravidae.
Conclusion and recommendations: We concluded that, maternally transferred antibodies (IgG) to full-length VAR2CSA in neonates decline markedly at 5 months of age. The magnitude of antibody response to full-length VAR2CSA in children aged 2-15 years is weak. Mothers’ pregnancy associated malaria status and parity influence the level of antibodies in neonates. We humbly recommend to the ministry of health, together with the scientific community, to carry-out a study in a larger scale to have a better understanding on the kinetics and dynamics of the antibodies to VAR2CSA in children.