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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

Antibody levels over gestation could be classified as relatively stable or dynamic. For each individual woman, the mean antibody response over gestation time and standard deviation (SD; ie, how far the individuals IgG response fluctuated from their mean response) was calculated. Use of a cutoff of a SD of 0.1 broadly classified individual woman as having dynamic (SD ≥ 0.1) or relatively stable responses (SD < 0.1). (A) The categorization of relatively stable and dynamic responses to PfAMA1 is shown as a representative example of antimalarial IgG responses throughout pregnancy (each line represents antibody levels in an individual over time). (B) The proportion (%) of dynamic antibody responses according to longitudinal exposure group. Species-specific cases refers to women who were infected with Plasmodium falciparum or Plasmodium vivax during pregnancy for P. falciparum and P. vivax antigens, respectively. The proportion of women with dynamic responses during pregnancy was associated with species-specific longitudinal exposure groups PfVAR2CSA, P < .001; PfAMA1, P < .001; PfEBA175 P = .24; PfMSP2, P < .001; PfMSP3, P < .001; PvAMA, P = .006.
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JIS566F2: Antibody levels over gestation could be classified as relatively stable or dynamic. For each individual woman, the mean antibody response over gestation time and standard deviation (SD; ie, how far the individuals IgG response fluctuated from their mean response) was calculated. Use of a cutoff of a SD of 0.1 broadly classified individual woman as having dynamic (SD ≥ 0.1) or relatively stable responses (SD < 0.1). (A) The categorization of relatively stable and dynamic responses to PfAMA1 is shown as a representative example of antimalarial IgG responses throughout pregnancy (each line represents antibody levels in an individual over time). (B) The proportion (%) of dynamic antibody responses according to longitudinal exposure group. Species-specific cases refers to women who were infected with Plasmodium falciparum or Plasmodium vivax during pregnancy for P. falciparum and P. vivax antigens, respectively. The proportion of women with dynamic responses during pregnancy was associated with species-specific longitudinal exposure groups PfVAR2CSA, P < .001; PfAMA1, P < .001; PfEBA175 P = .24; PfMSP2, P < .001; PfMSP3, P < .001; PvAMA, P = .006.

Mentions: The weekly surveillance for Plasmodium species was coupled with regular antibody determination throughout pregnancy. Antibody responses were assessed from median 10 weeks gestation to delivery in case subjects (in a Plasmodium species–specific manner) and in uninfected control subjects comprising a selection of antibody high schizont lysate responders and low responders. Antibodies to Schizont lysate were used as a marker of exposure to blood-stage malaria. In all longitudinal exposure groups, IgG antibody responses in each woman showed complex dynamics over gestation time. Women could be broadly classified as having dynamic or relatively stable responses (defined as an individual standard deviation ≥0.1 or <0.1, respectively) (Figure 2A). In addition, among individual women, differences in the patterns or dynamics of responses to different antigens over time also varied (Figure 3), because women could have highly fluctuant responses to ≥1 antigen but relatively stable responses to other antigens. Overall, case subjects were more likely to have dynamic fluctuating antibody responses specific to the infecting Plasmodium species during pregnancy, compared with uninfected women (except for responses to PfMSP2) (Figure 2B). Of interest, a substantial proportion of women demonstrated dynamic responses, even in the absence of detectable Plasmodium infection during pregnancy (Figure 2B), suggesting that exposure to Plasmodium species is not the only factor that determines fluctuations in antibody levels over time.Figure 2.


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)

Antibody levels over gestation could be classified as relatively stable or dynamic. For each individual woman, the mean antibody response over gestation time and standard deviation (SD; ie, how far the individuals IgG response fluctuated from their mean response) was calculated. Use of a cutoff of a SD of 0.1 broadly classified individual woman as having dynamic (SD ≥ 0.1) or relatively stable responses (SD < 0.1). (A) The categorization of relatively stable and dynamic responses to PfAMA1 is shown as a representative example of antimalarial IgG responses throughout pregnancy (each line represents antibody levels in an individual over time). (B) The proportion (%) of dynamic antibody responses according to longitudinal exposure group. Species-specific cases refers to women who were infected with Plasmodium falciparum or Plasmodium vivax during pregnancy for P. falciparum and P. vivax antigens, respectively. The proportion of women with dynamic responses during pregnancy was associated with species-specific longitudinal exposure groups PfVAR2CSA, P < .001; PfAMA1, P < .001; PfEBA175 P = .24; PfMSP2, P < .001; PfMSP3, P < .001; PvAMA, P = .006.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

JIS566F2: Antibody levels over gestation could be classified as relatively stable or dynamic. For each individual woman, the mean antibody response over gestation time and standard deviation (SD; ie, how far the individuals IgG response fluctuated from their mean response) was calculated. Use of a cutoff of a SD of 0.1 broadly classified individual woman as having dynamic (SD ≥ 0.1) or relatively stable responses (SD < 0.1). (A) The categorization of relatively stable and dynamic responses to PfAMA1 is shown as a representative example of antimalarial IgG responses throughout pregnancy (each line represents antibody levels in an individual over time). (B) The proportion (%) of dynamic antibody responses according to longitudinal exposure group. Species-specific cases refers to women who were infected with Plasmodium falciparum or Plasmodium vivax during pregnancy for P. falciparum and P. vivax antigens, respectively. The proportion of women with dynamic responses during pregnancy was associated with species-specific longitudinal exposure groups PfVAR2CSA, P < .001; PfAMA1, P < .001; PfEBA175 P = .24; PfMSP2, P < .001; PfMSP3, P < .001; PvAMA, P = .006.
Mentions: The weekly surveillance for Plasmodium species was coupled with regular antibody determination throughout pregnancy. Antibody responses were assessed from median 10 weeks gestation to delivery in case subjects (in a Plasmodium species–specific manner) and in uninfected control subjects comprising a selection of antibody high schizont lysate responders and low responders. Antibodies to Schizont lysate were used as a marker of exposure to blood-stage malaria. In all longitudinal exposure groups, IgG antibody responses in each woman showed complex dynamics over gestation time. Women could be broadly classified as having dynamic or relatively stable responses (defined as an individual standard deviation ≥0.1 or <0.1, respectively) (Figure 2A). In addition, among individual women, differences in the patterns or dynamics of responses to different antigens over time also varied (Figure 3), because women could have highly fluctuant responses to ≥1 antigen but relatively stable responses to other antigens. Overall, case subjects were more likely to have dynamic fluctuating antibody responses specific to the infecting Plasmodium species during pregnancy, compared with uninfected women (except for responses to PfMSP2) (Figure 2B). Of interest, a substantial proportion of women demonstrated dynamic responses, even in the absence of detectable Plasmodium infection during pregnancy (Figure 2B), suggesting that exposure to Plasmodium species is not the only factor that determines fluctuations in antibody levels over time.Figure 2.

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