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New insights into acquisition, boosting, and longevity of immunity to malaria in pregnant women.

Fowkes FJ, McGready R, Cross NJ, Hommel M, Simpson JA, Elliott SR, Richards JS, Lackovic K, Viladpai-Nguen J, Narum D, Tsuboi T, Anders RF, Nosten F, Beeson JG - J. Infect. Dis. (2012)

Bottom Line: Antibodies to P. falciparum and P. vivax were highly variable over time, and maintenance of high levels of antimalarial antibodies involved highly dynamic responses resulting from intermittent exposure to infection.The longer half-life of antibodies to PfVAR2CSA suggests that antibodies acquired in one pregnancy may be maintained to protect subsequent pregnancies.These findings may have important practical implications for predicting the duration of vaccine-induced responses by candidate antigens and supports the development of malaria vaccines to protect pregnant women.

View Article: PubMed Central - PubMed

Affiliation: Macfarlane Burnet Institute of Medical Research, Melbourne, Australia. fowkes@burnet.edu.au

ABSTRACT

Background: How antimalarial antibodies are acquired and maintained during pregnancy and boosted after reinfection with Plasmodium falciparum and Plasmodium vivax is unknown.

Methods: A nested case-control study of 467 pregnant women (136 Plasmodium-infected cases and 331 uninfected control subjects) in northwestern Thailand was conducted. Antibody levels to P. falciparum and P. vivax merozoite antigens and the pregnancy-specific PfVAR2CSA antigen were determined at enrollment (median 10 weeks gestation) and throughout pregnancy until delivery.

Results: Antibodies to P. falciparum and P. vivax were highly variable over time, and maintenance of high levels of antimalarial antibodies involved highly dynamic responses resulting from intermittent exposure to infection. There was evidence of boosting with each successive infection for P. falciparum responses, suggesting the presence of immunological memory. However, the half-lives of Plasmodium antibody responses were relatively short, compared with measles (457 years), and much shorter for merozoite responses (0.8-7.6 years), compared with PfVAR2CSA responses (36-157 years). The longer half-life of antibodies to PfVAR2CSA suggests that antibodies acquired in one pregnancy may be maintained to protect subsequent pregnancies.

Conclusions: These findings may have important practical implications for predicting the duration of vaccine-induced responses by candidate antigens and supports the development of malaria vaccines to protect pregnant women.

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Related in: MedlinePlus

Antibodies to Plasmodium species blood-stage antigens at enrollment. Antibody levels were determined in all available case (n = 124) and control (n = 320) samples at enrollment (median 10 weeks gestation). (A) Seroprevalence with standard errors and (B) boxplots of antibody levels in case and control subjects. Horizontal lines represent medians, boxes represent interquartile range, and lines represent ranges with outliers represented as dots. Antibody prevalences and levels were significantly higher in case than in control subjects (P < .001). Antibody levels according to gravidity in control subjects (C) and case subjects (D). In case and control groups, there was no association between gravidity and antibody levels (P > .17).
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JIS566F1: Antibodies to Plasmodium species blood-stage antigens at enrollment. Antibody levels were determined in all available case (n = 124) and control (n = 320) samples at enrollment (median 10 weeks gestation). (A) Seroprevalence with standard errors and (B) boxplots of antibody levels in case and control subjects. Horizontal lines represent medians, boxes represent interquartile range, and lines represent ranges with outliers represented as dots. Antibody prevalences and levels were significantly higher in case than in control subjects (P < .001). Antibody levels according to gravidity in control subjects (C) and case subjects (D). In case and control groups, there was no association between gravidity and antibody levels (P > .17).

Mentions: There were 136 case subjects (women infected with P. falciparum and/or P. vivax during pregnancy) and 331 control subjects (women not infected with Plasmodium) included in a nested case-control study evaluating the association between antibody responses and Plasmodium infection during pregnancy (Table 1). A total of 1948 samples were tested for antibodies to 7 different Plasmodium antigens. Antigens were selected on the basis of whether they are targets of protective immunity or biomarkers of immunity [6, 24], include antigens of P. falciparum and P. vivax, and represent antigens of merozoites and IEs. At enrollment (median gestational age, 9.8 weeks [interquartile range (IQR), 7.0–13.9 weeks] for case subjects and 9.56 weeks [IQR, 7.6–11.6 weeks] for control subjects) (Table 1), the prevalence and levels of anti–P. falciparum and P. vivax blood-stage antibodies were higher in case subjects than in control subjects (P < .0001) (Figure 1A and B), indicative of increased Plasmodium infection before enrollment (Table 1). Although multigravida exhibited some of the highest antibody responses, median levels of merozoite and pregnancy-specific antibodies were comparable to primigravida in case and control subjects (P > .17) (Figure 1C and D). P. falciparum antibody responses were strongly correlated with each other (ρ=0.45–0.87; P < .001) and less strongly with P. vivax responses (ρ=0.31–0.52; P < .001).Table 1.


New insights into acquisition, boosting, and longevity of immunity to malaria in pregnant women.

Fowkes FJ, McGready R, Cross NJ, Hommel M, Simpson JA, Elliott SR, Richards JS, Lackovic K, Viladpai-Nguen J, Narum D, Tsuboi T, Anders RF, Nosten F, Beeson JG - J. Infect. Dis. (2012)

Antibodies to Plasmodium species blood-stage antigens at enrollment. Antibody levels were determined in all available case (n = 124) and control (n = 320) samples at enrollment (median 10 weeks gestation). (A) Seroprevalence with standard errors and (B) boxplots of antibody levels in case and control subjects. Horizontal lines represent medians, boxes represent interquartile range, and lines represent ranges with outliers represented as dots. Antibody prevalences and levels were significantly higher in case than in control subjects (P < .001). Antibody levels according to gravidity in control subjects (C) and case subjects (D). In case and control groups, there was no association between gravidity and antibody levels (P > .17).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475637&req=5

JIS566F1: Antibodies to Plasmodium species blood-stage antigens at enrollment. Antibody levels were determined in all available case (n = 124) and control (n = 320) samples at enrollment (median 10 weeks gestation). (A) Seroprevalence with standard errors and (B) boxplots of antibody levels in case and control subjects. Horizontal lines represent medians, boxes represent interquartile range, and lines represent ranges with outliers represented as dots. Antibody prevalences and levels were significantly higher in case than in control subjects (P < .001). Antibody levels according to gravidity in control subjects (C) and case subjects (D). In case and control groups, there was no association between gravidity and antibody levels (P > .17).
Mentions: There were 136 case subjects (women infected with P. falciparum and/or P. vivax during pregnancy) and 331 control subjects (women not infected with Plasmodium) included in a nested case-control study evaluating the association between antibody responses and Plasmodium infection during pregnancy (Table 1). A total of 1948 samples were tested for antibodies to 7 different Plasmodium antigens. Antigens were selected on the basis of whether they are targets of protective immunity or biomarkers of immunity [6, 24], include antigens of P. falciparum and P. vivax, and represent antigens of merozoites and IEs. At enrollment (median gestational age, 9.8 weeks [interquartile range (IQR), 7.0–13.9 weeks] for case subjects and 9.56 weeks [IQR, 7.6–11.6 weeks] for control subjects) (Table 1), the prevalence and levels of anti–P. falciparum and P. vivax blood-stage antibodies were higher in case subjects than in control subjects (P < .0001) (Figure 1A and B), indicative of increased Plasmodium infection before enrollment (Table 1). Although multigravida exhibited some of the highest antibody responses, median levels of merozoite and pregnancy-specific antibodies were comparable to primigravida in case and control subjects (P > .17) (Figure 1C and D). P. falciparum antibody responses were strongly correlated with each other (ρ=0.45–0.87; P < .001) and less strongly with P. vivax responses (ρ=0.31–0.52; P < .001).Table 1.

Bottom Line: Antibodies to P. falciparum and P. vivax were highly variable over time, and maintenance of high levels of antimalarial antibodies involved highly dynamic responses resulting from intermittent exposure to infection.The longer half-life of antibodies to PfVAR2CSA suggests that antibodies acquired in one pregnancy may be maintained to protect subsequent pregnancies.These findings may have important practical implications for predicting the duration of vaccine-induced responses by candidate antigens and supports the development of malaria vaccines to protect pregnant women.

View Article: PubMed Central - PubMed

Affiliation: Macfarlane Burnet Institute of Medical Research, Melbourne, Australia. fowkes@burnet.edu.au

ABSTRACT

Background: How antimalarial antibodies are acquired and maintained during pregnancy and boosted after reinfection with Plasmodium falciparum and Plasmodium vivax is unknown.

Methods: A nested case-control study of 467 pregnant women (136 Plasmodium-infected cases and 331 uninfected control subjects) in northwestern Thailand was conducted. Antibody levels to P. falciparum and P. vivax merozoite antigens and the pregnancy-specific PfVAR2CSA antigen were determined at enrollment (median 10 weeks gestation) and throughout pregnancy until delivery.

Results: Antibodies to P. falciparum and P. vivax were highly variable over time, and maintenance of high levels of antimalarial antibodies involved highly dynamic responses resulting from intermittent exposure to infection. There was evidence of boosting with each successive infection for P. falciparum responses, suggesting the presence of immunological memory. However, the half-lives of Plasmodium antibody responses were relatively short, compared with measles (457 years), and much shorter for merozoite responses (0.8-7.6 years), compared with PfVAR2CSA responses (36-157 years). The longer half-life of antibodies to PfVAR2CSA suggests that antibodies acquired in one pregnancy may be maintained to protect subsequent pregnancies.

Conclusions: These findings may have important practical implications for predicting the duration of vaccine-induced responses by candidate antigens and supports the development of malaria vaccines to protect pregnant women.

Show MeSH
Related in: MedlinePlus