IgG and IgM responses to the Plasmodium falciparum asexual stage antigens reflect respectively protection against malaria during pregnancy and infanthood

Abstract

Background: Plasmodium falciparum malaria is a public health issue mostly seen in tropical countries. Until now, there is no effective malaria vaccine against antigens specific to the blood-stage of P. falciparum infection. Because the pathogenesis of malarial disease results from blood-stage infection, it is essential to identify the most promising blood-stage vaccine candidate antigens under natural exposure to malaria infection.

Methods: A cohort of 400 pregnant women and their infants was implemented in South Benin. An active and passive protocol of malaria surveillance was established during pregnancy and infancy to precisely ascertain malaria infections during the follow-up. Twenty-eight antibody (Ab) responses specific to seven malaria candidate vaccine antigens were repeatedly quantified during pregnancy (3 time points) and infancy (6 time points) in order to study the Ab kinetics and their protective role. Abs were quantified by ELISA and logistic, linear and cox-proportional hazard model were performed to analyse the associations between Ab responses and protection against malaria in mothers and infants, taking into account socio-economic factors and for infants an environmental risk of exposure.

Results: The levels of IgM against MSP1, MSP2 and MSP3 showed an early protective response against the onset of symptomatic malaria infections starting from the 18th month of life, whereas no association was found for IgG responses during infancy. In women, some IgG responses tend to be associated with a protection against malaria risk along pregnancy and at delivery, among them IgG3 against GLURP-R0 and IgG2 against MSP1.

Conclusion: The main finding suggests that IgM should be considered in vaccine designs during infanthood. Investigation of the functional role played by IgM in malaria protection needs further attention.

Keywords: Plasmodium falciparum; Asexual stage; IgG; IgM; Infancy; Pregnancy.

Fig. 1

Antibody kinetics during pregnancy and at birth. Overview of the specific asexual stage antigens IgG1, IgG2, IgG3, and IgM Ab concentrations (pg/mL, median and range) against the AMA1, GLURP-R0, GLURP-R2, MSP1, MSP2-3D7, MSP2-FC27 and MSP3 antigens in mothers at the antenatal visits (ANV1 and ANV2), at delivery (DEL) and at birth (BIR, cord blood). The Significant p-value is (p < 0.05). Nominal p-value levels are indicated by: p < 0.1; *p < 0.05; ** p < 0.01; *** p < 0.001. Colored dots in each column indicate individual data points and their distribution. Only differences in IgGs levels between mother at delivery (DEL) and newborn at birth (BIR) analyzed by paired t-test are shown in the figure. IgM levels difference between delivery (DEL) and birth (BIR) are not shown, as it is known that there is no transfer of IgM from mother to newborn. Using Tukey's pairwise method, the differences in other antibody levels at each time point with reference to the start point are summarized in Additional file 2: Table S2

Fig. 2

Antibody kinetics during infancy. Overview of the specific asexual stage antigens IgG1, IgG2, IgG3, and IgM Ab concentrations (pg/mL, median and range) against the AMA1, GLURP-R0, GLURP-R2, MSP1, MSP2-3D7, MSP2-FC27 and MSP3 antigens in infants from birth (BIR, cord blood) until the age of two years (at 6, 9, 12, 18, and 24 months). Colored dots in each column indicate individual data points and their distribution. Using Tukey's pairwise method, the differences in other antibody levels at each time point with reference to the start point are summarized in Additional file 2: Table S2

Fig. 3

A Maternal antibodies protection against peripheral malaria infections during pregnancy. Hazard ratios (HR) and 95% confidence intervals obtained from a Cox regression model are represented for each Ab responses measured at ANV2. A hazard ratio < 1 indicates that Ab response is associated with a decrease risk of malaria infection; whereas a hazard ratio > 1 indicates that Ab response is associated with a higher risk of malaria infection. Analyses were adjusted on the transmission season at the time of ANV2 (dry versus rainy season), malaria infection before ANV2, gravidity status (Primigravidity versus Multigravidity) and the possession of TV. B Maternal antibodies protection against placental malaria infection. Odds ratios (OR) and 95% confidence are represented for each Ab responses measured at ANV2. An odd ratio < 1 indicates that Ab response is associated with a decrease risk of placental malaria infection at delivery. Results were adjusted on the ethnic groups and age group of the mothers. For both, significant p-values are (p < 0.05) and levels of nominal p-values are indicated by: •p < 0.1; *p < 0.05; ** p < 0.01; ***p < 0.001