Acquisition of antibodies to variant antigens on the surface of Plasmodium falciparum-infected erythrocytes during pregnancy

Abstract

Pregnancy-associated malaria is characterized by Plasmodium falciparum adherence to chondroitin sulfate A (CSA) in placenta, through a particular variant surface antigen (VSA). VSA_CSA-specific IgG are involved in protection against placental malaria. In order to assess the relationship between VSA_CSA-specific antibody responses and parity as well as protection against placental malaria, the occurrence of P. falciparum infection was assessed in 306 pregnant women from a low malaria transmission area of Senegal. Anti-VSA_CSA antibodies against three placental parasite isolates were measured by flow cytometry, at enrollment and delivery. Placental infection prevalence rates were highest in primigravidae, but no clear decreasing trend was observed from the second pregnancy onwards. Anti-VSA_CSA antibody prevalence rates increased with parity. Both anti-VSA_CSA antibody prevalence rates and levels increased during pregnancy only in women infected with P. falciparum. Although a single or a very limited number of P. falciparum infections were able to induce an anti-VSA_CSA antibody response, the level or the quality of this response did not appear to confer protection against placental malaria infection.

Introduction

In Plasmodium falciparum endemic areas, previously immune women become more susceptible to malaria during their first pregnancy. The prevalence rates of peripheral and placental parasitemias, as well as their densities, are highest in primigravidae (Brabin, 1983, Steketee et al., 1988), decreasing after the second pregnancy. Pregnancy-associated malaria (PAM) is characterized by the accumulation of infected red blood cells (IRBC) in the placenta (Fried and Duffy, 1996). PAM is responsible for low birth weight, abortion and maternal mortality (Menendez et al., 2000). Chondroitin sulfate A (CSA) expressed on syncytiotrophoblast mediates the adherence of IRBC to placenta (Fried and Duffy, 1996) in association with the expression of a distinct variant surface antigen (VSA) on the membrane of IRBC. The major falciparum antigen involved is the variant P. falciparum erythrocyte membrane protein-1 (PfEMP1), each variant mediating adhesion of IRBC to a specific host molecule (Buffet et al., 1999). PAM is caused by P. falciparum which express peculiar VSAs (VSA_CSA) that allow the parasite to bind CSA and sequester in the placenta (Rogerson et al., 1995). Conversely to the VSA expressed by parasites infecting non-pregnant hosts, these VSA_CSA are reasonably conserved antigens (Khattab et al., 2003). In areas of intense malaria transmission, antibody levels to VSA_CSA increase with gravidity, block the adhesion of IRBC to CSA (Fried et al., 1998, Gysin et al., 1999, Maubert et al., 1999, O’Neil-Dunne et al., 2001), and protect against low birth weight and maternal anemia (Staalsoe et al., 2004). A placental infection during first pregnancy was suggested to induce a substantial antibody response to CSA-binding IRBC (Beeson et al., 2004), raising hope for a potential VSA-based vaccine against PAM. Studies reported that anti-VSA_CSA-specific antibodies are not acquired earlier than halfway through the first pregnancy (O’Neil-Dunne et al., 2001, Staalsoe et al., 2001). In the present work, we aimed to investigate the relationships between parity, placental infection and presence of anti-VSA_CSA antibody. In addition, we assessed the relation between the occurrence of P. falciparum infections during pregnancy and the development of an anti-VSA_CSA antibody response against three different placental isolates.