Effects of sex, parity, and sequence variation on seroreactivity to candidate pregnancy malaria vaccine antigens.

Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
The Journal of Infectious Diseases (Impact Factor: 5.78). 08/2007; 196(1):155-64. DOI: 10.1086/518513
Source: PubMed

ABSTRACT Plasmodium falciparum-infected erythrocytes adhere to chondroitin sulfate A (CSA) to sequester in the human placenta, and pregnancy malaria (PM) is associated with the development of disease in and the death of both mother and child. A PM vaccine appears to be feasible, because women become protected as they develop antibodies against placental infected erythrocytes (IEs). Two IE surface molecules, VAR1CSA and VAR2CSA, bind CSA in vitro and are potential vaccine candidates.
We expressed all domains of VAR1CSA and VAR2CSA as mammalian cell surface proteins, using a novel approach that allows rapid purification, immobilization, and quantification of target antigen. For serum samples from East Africa, we measured reactivity to all domains, and we examined the effects of host sex and parity, as well as the effects of parasite antigenic variation.
Serum samples obtained from multigravid women had a higher reactivity to all VAR2CSA domains than did those obtained from primigravid women or from men. Conversely, serum samples obtained from men had consistently higher reactivity to VAR1CSA domains than did those obtained from gravid women. Seroreactivity was strongly influenced by antigenic variation of VAR2CSA Duffy binding-like domains.
Women acquire antibodies to VAR2CSA over successive pregnancies, but they lose reactivity to VAR1CSA. Serum reactivity to VAR2CSA is variant specific, and future studies should examine the degree to which functional antibodies, such as binding-inhibition antibodies, are variant specific.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In pregnancy, parity-dependent immunity is observed in response to placental infection with Plasmodium falciparum. Antibodies recognize the surface antigen, VAR2CSA, expressed on infected red blood cells and inhibit cytoadherence to the placental tissue. In most malaria-endemic settings, antibodies against VAR2CSA are predominantly observed in multigravid women, and infrequently in men, children, and nulligravid women. However, in Colombia, we detected antibodies against multiple constructs of VAR2CSA among men and children with acute P. falciparum and P. vivax infection. The majority of men and children (>60%) had high levels of IgGs against three recombinant domains of VAR2CSA: DBL5ε, DBL3X and ID1-ID2. Surprisingly, these antibodies were observed in pregnant women, men and children only exposed to P. vivax. Moreover, the anti-VAR2CSA antibodies are of high avidity and efficiently inhibit adherence of infected red blood cells to chondroitin sulphate A in vitro, suggesting that they are specific and functional. These unexpected results suggest there may be genotypic or phenotypic differences in the parasites of this region, or in the host response to either P. falciparum or P. vivax infection outside of pregnancy. These findings may hold significant clinical relevance to the pathophysiology and outcome of malaria infections in this region.
    Infection and immunity 03/2014; · 4.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasmodium falciparum infection during pregnancy contributes substantially to malaria burden in both mothers and offspring. Analysis of naturally acquired immune responses that confer protection against parasitemia and clinical disease is important to guide vaccine evaluation as well as identify immune correlates. Unfortunately, few studies have addressed the relationship between immune responses to malaria vaccine candidate antigens and protection against adverse effects on pregnant women and newborn birth weight. This study examines the relationship of maternal antibody responses to serine repeat antigen-5 (SE36) and merozoite surface protein-1 (MSP119 and MSP142) with placental parasitemia and birth weight. In a peri-urban setting in Uganda, pregnant women without placental parasites have high median ODs for antibodies against SE36 (P < 0.001). Naturally acquired anti-SE36 IgG was most prevalent in women without placental parasitemia (P < 0.001). Furthermore, pregnant women with significantly high levels of anti-SE36 IgG delivered babies with normal birth weights (P < 0.001). That antibody to SE36 was associated with both a reduced risk of placental parasitemia and resulting normal birth weight in newborns suggests some protective role. In contrast, although antibody to MSP142 was also associated with reduced placental parasitemia and immune responses to both MSP119 and MSP142 may be of importance, there was no association between anti-MSP119 antibodies and infant birth weight outcomes. This study highlights the need for conducting further studies to investigate the association of antibodies against SE36 and outcomes of malaria infection in pregnant women.
    Parasitology International 06/2013; 62(3):237–239. · 2.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pregnant women have an increased risk of malaria infection, independent of previously acquired immunity. Women in their first pregnancy and children under the age of five are the primary victims of malaria worldwide. Pregnant women develop antibodies against placenta-adhesive parasites in a parity-dependent manner. Various efforts to understand the targets, quality, and quantity of this antibody response could aid the design of an effective vaccine against placental malaria. This review focuses on the research that has led to the current understanding of the antibody response that primigravidae (PG) acquire to Plasmodium falciparum malaria and draws from this knowledge to suggest serology and PG as sentinels for malaria transmission.
    Trends in Parasitology 12/2013; · 6.22 Impact Factor


Available from
Jun 6, 2014