Association of Antibodies to VAR2CSA and Merozoite Antigens with Pregnancy Outcomes in Women Living in Yaoundé, Cameroon

Abstract

infections are serious in pregnant women, because VAR2CSA allows parasitized erythrocytes to sequester in the placenta, causing placental malaria (PM). In areas of endemicity, women have substantial malarial immunity prior to pregnancy, including antibodies to merozoite antigens, but produce antibodies to VAR2CSA only during pregnancy. The current study sought to determine the importance of antibodies to VAR2CSA and merozoite antigens in pregnant women in Yaoundé, Cameroon, where malaria transmission was relatively low. A total of 1,377 archival plasma samples collected at delivery were selected (at a 1:3 ratio of PM-positive [PM+] to PM-negative [PM-] women) and screened for antibodies to full-length VAR2CSA and 7 merozoite antigens. Results showed that many PM+ women and most PM- women lacked antibodies to VAR2CSA at delivery. Among PM+ women, antibodies to VAR2CSA were associated with a reduced risk of having high placental parasitemia (odds ratio [OR], 0.432; confidence interval [CI], 0.272, 0.687; = 0.0004) and low-birth-weight (LBW) babies (OR = 0.444; CI, 0.247, 0.799; = 0.0068), even during first pregnancies. Among antibodies to the 7 merozoite antigens, i.e., AMA1, EBA-175, MSP1, MSP2, MSP3, MSP11, and Pf41, only antibodies to MSP3, EBA-175, and Pf41 were associated with reduced risk for high placental parasitemias ( = 0.0389, 0.0291, and 0.0211, respectively) and antibodies to EBA-175 were associated with reduced risk of premature deliveries ( = 0.0211). However, after adjusting for multiple comparisons significance declined. Thus, in PM+ women, antibodies to VAR2CSA were associated with lower placental parasitemias and reduced prevalence of LBW babies in this low-transmission setting.

Antibodies to full-length and the DBL5 domain of VAR2CSA in pregnant women after long-term implementation of intermittent preventive treatment in Etoudi, Cameroon

“…In fact, among the 104 PM-women at delivery only 31.7% and 30.8% had Ab to FV2 and DBL5 respectively, and only 12.5% of paucigravidae and 48% of MG had Ab to FV2 (Table 2). Although pre-IPT Ab prevalence in Etoudi is unknown, Ab prevalence to FV2 in PM-women living in Yaoundé prior to implementation was 24.3% in pauci-and 40.1% in MG [20]. Thus, with decreased transmission and extended use of IPT, today fewer women have Ab to FV2 during their first two pregnancies, but Ab prevalence is similar in MG.…”

“…Within a given pattern, some variation is also observed; for example, in the equatorial pattern where this study was carried out, the transmission increases from the center urban to rural areas. Available data on Ab response to VAR2CSA in Cameroonian women exist only for central urban (low malaria transmission) [20,21] or rural area (high malaria transmission) [14,15,22,23], although these areas are usually separated by a peri-urban or sub-urban area where malaria transmission is intermediate or relatively low. In addition, most of previous studies on Ab response to VAR2CSA in Cameroon were carried out before the IPTp-SP implementation.…”

Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review

“…We found that positive antibody responses to pregnancy-specific antigens were associated with increased odds of peripheral infection in some studies, with varying degrees of significance [43,55,57,61]. At delivery, antibody responders (IgG) to the pRBC surface [35,53,61], to full-length VAR2CSA (FV2) [52,60], and to the vaccine candidate ID1-ID2a, which includes interdomain region 1, DBL2X, and interdomain region 2a, had increased odds of placental infection compared to non-responders [42,52] (Fig. 2a).…”

“…2a). Antibody responders to FV2, and VAR2CSA domains, with the exception of DBL4, had increased odds of placental infection compared to nonresponders [42,52,59,60,63] (Fig. 2a).…”

“…We included estimates from nine studies that investigated the association between antibodies (Abs) to pregnancy-specific pRBC or VAR2CSA domains measured at delivery, and placental infection ( Fig. 2a) [35,42,52,53,56,[59][60][61]63]. In all studies, placental infection was confirmed by slide microscopy of placental blood or placental histology.…”