Abstract. A prospective longitudinal study of Plasmodium falciparum in pregnant women was conducted in the rural village of Ngali II, where malaria is hyperendemic and individuals receive ~0.7 infectious mosquito bites/person/day throughout the year. Pregnant women ( N = 60; 19 primigravidae, 41 multigravidae) were enrolled early in pregnancy (median 14 wk) and were followed monthly, with 38 women followed through term (5.7 ± 1.1 prenatal visits and delivery). The total number of times primigravidae were slide-positive during pregnancy was higher than multigravidae (3.3 ± 1.1 versus 1.3 ± 1.3 times; P < 0.001), but no difference in the number of polymerase chain reaction-positive cases (4.6 ± 1.7 and 3.4 ± 1.7 times, P = 0.106) or total genotypes they harbored (8.9 ± 3.2 and 7.0 ± 2.9) was found. Only 7.9% women developed symptomatic infections. All primigravidae and 38% multigravidae were placental malaria-positive at delivery ( P = 0.009). Genotyping showed that 77% of placental parasites were acquired ≥ 30 wks in pregnancy. These results help identify the extent of malaria-associated changes women experience during pregnancy.

In pregnant women, Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8–9% of males had antibodies to full-length VAR2CSA, but 90–96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a.

Myostatin, a member of the transforming growth factor-beta (TGF-beta) superfamily, is a potent negative regulator of skeletal muscle growth. The objective of this study was to produce a monoclonal anti-myostatin antibody and to examine the effects of in ovo administration of the antibody on posthatch broiler growth and muscle mass. The mature form of myostatin was expressed in Escherichia coli and used as an immunogen in producing a monoclonal antibody against myostatin. One hybridoma clone (mAb-c134) that showed the strongest affinity to the immunogen in Western blot analysis was used in producing a large quantity of monoclonal anti-myostatin antibody. In Western blot analysis, this antibody showed a strong binding affinity to commercially available mature myostatin and demonstrated a certain level of cross-reactivity with recombinant human BMP2 but not with recombinant human TGF-beta3 or porcine TGF-beta1. Competitive ELISA demonstrated binding of the antibody to the native form of mature myostatin in solution. To examine the effects of in ovo administration of the mAb-c134 antibody, eggs were injected once with 40 microg of mAb-c134 in 50 mL of PBS either into the albumen or yolk on d 3 of incubation. Controls received no injection. After hatching, chicks were raised for 35 d. Broilers from eggs that had the antibody injected into the yolk had significantly heavier body (4.2%) and muscle (5.5%) mass than the controls in both male and female birds. In contrast, no significant effects on body and muscle mass were observed when the mAb-c134 antibody was injected into the albumen. The results of this study suggest that immunoneutralization of myostatin during embryonic development is a potential means to improve growth potential of broilers.

Placental malaria infections are caused by Plasmodium falciparum-infected red blood cells sequestering in the placenta by binding to chondroitin sulfate A, mediated by VAR2CSA, a variant of the PfEMP1 family of adhesion antigens. Recent studies have shown that many P. falciparum genomes have multiple genes coding for different VAR2CSA proteins, and parasites with >1 var2csa gene appear to be more common in pregnant women with placental malaria than in nonpregnant individuals. We present evidence that, in pregnant women, parasites containing multiple var2csa-type genes possess a selective advantage over parasites with a single var2csa gene. Accumulation of parasites with multiple copies of the var2csa gene during the course of pregnancy was also correlated with the development of antibodies involved in blocking VAR2CSA adhesion. The data suggest that multiplicity of var2csa-type genes enables P. falciparum parasites to persist for a longer period of time during placental infections, probably because of their greater capacity for antigenic variation and evasion of variant-specific immune responses.

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.