Antibodies That Inhibit Binding of Plasmodium falciparum -Infected Erythrocytes to Chondroitin Sulfate A and to the C Terminus of Merozoite Surface Protein 1 Correlate with Reduced Placental Malaria in Cameroonian Women

Abstract

Plasmodium falciparum-infected erythrocytes often sequester in the placenta of pregnant women, producing placental malaria, a condition that can compromise the health of the developing fetus. Scientists are hopeful that a vaccine can be developed to prevent this condition. Immunological mechanisms responsible for eliminating parasites from the placenta remain unclear, but antibodies to the carboxyl-terminal 19-kDa segment of the merozoite surface protein 1 (MSP1-19), the ring-infected erythrocyte surface antigen (RESA), and an erythrocytesurface ligand that binds chondroitin sulfate A (CSA-L) have been implicated. In addition, antibodies to sporozoite and liver-stage antigens could reduce initial parasite burdens. This study sought to determine if antibodies to the circumsporozoite protein (CSP), liver-stage antigen 1 (LSA1), RESA, MSP1-19, or CSA-L correlated with either the absence of placental parasites or low placental parasitemias. Using a frequency-matched case-control study design, we compared antibody levels in women (gravidity 1 to 11) with and without placental malaria. Results showed that women who were antibody negative for MSP1-19 were at a higher risk of having placental malaria than women with antibodies (P < 0.007). Furthermore, an association between high levels of antibodies that blocked the binding of infected erythrocytes to CSA and low placental parasitemias was observed (P ‫؍‬ 0.02). On the other hand, women with high antibody levels at term to CSP, LSA1, and RESA were more likely to have placental malaria than antibody-negative women. Since antibodies to MSP1-19 and CSA-L were associated with reduced placental malaria, both antigens show promise for inclusion in a vaccine for women of child-bearing age.

Effects of Pregnancy and Intensity of Plasmodium falciparum Transmission on Immunoglobulin G Subclass Responses to Variant Surface Antigens

“…This corresponds well with the finding that VSA PAM -specific IgG responses appear around weeks 18 to 20 in primigravidae and somewhat earlier in multigravidae (22,30). The weak, but highly significant, negative association between VSA PAM -specific IgG3 and gestational age that we found in samples from Yaounde may thus reflect catabolic antibody decay toward the end of pregnancy following VSA PAM -specific antibody-mediated control of placental parasite multiplication (11,(30)(31)(32). The fact that this was not seen for IgG1 was probably related to the longer half-life of this subclass, and the fact that it was not seen in the samples from Etoa may be related to the higher endemicity, less drug usage (Table 1), and/or inadequate sample size.…”

Evaluation of oxidative stress and antioxidant status of pregnant women suffering from malaria in Cameroon

“…The presence of IRBCs frequently induces the infiltration of inflammatory-type cells into the placenta, where they cause pathological alterations (26). It has been also shown that P. falciparum trophozoite infected human red cells produce H 2 O 2 and OH ¯ radical about twice as much as normal erythrocytes (17,27).…”

The Immunology and Pathogenesis of Malaria During Pregnancy

“…Titers of RESA-specific antibodies were lower in pregnant than non-pregnant women in some studies [129], but not others [52, 64], or were lower in primigravid than multigravid women in some studies [52,129], but not others [2,51]. Anti-RESA antibody levels by immunofluorescence or ELISA were inversely associated with parasitemia in some studies [8,129], but not others [52,184]. Higher levels of antibodies to merozoite surface protein 1 have also been associated with reduced risk of placental malaria in some studies [27,184] but not in others [76,126].…”