Limits...
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.

Show MeSH

Related in: MedlinePlus

Anti–Plasmodium falciparum levels increase with each successive P. falciparum infection. Multivariable linear mixed-effects modeling of the association between antibody levels and number of episodes in species-specific cases (n = 94 and n = 83 for P. falciparum and P. vivax analysis, respectively). The coefficients (95% confidence interval [CI]) for the estimated mean increase in antibody levels per increase in P. falciparum episode number were as follows: PfVAR2CSA 0.03 (0.01–0.05), P = .011; PfAMA1 0.05 (0.02–0.08), P < .001; PfEBA175 0.05 (0.02–0.07) P < .001; PfMSP2 0.02 (0.003–0.04), P = .025; PfMSP3 0.018 (−0.001 to 0.04), P = .063; PvAMA1 − 0.0004 (−0.01 to 0.01), P = .96; measles −0.003 (−0.015 to 0.01), P = .63.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3475637&req=5

JIS566F4: Anti–Plasmodium falciparum levels increase with each successive P. falciparum infection. Multivariable linear mixed-effects modeling of the association between antibody levels and number of episodes in species-specific cases (n = 94 and n = 83 for P. falciparum and P. vivax analysis, respectively). The coefficients (95% confidence interval [CI]) for the estimated mean increase in antibody levels per increase in P. falciparum episode number were as follows: PfVAR2CSA 0.03 (0.01–0.05), P = .011; PfAMA1 0.05 (0.02–0.08), P < .001; PfEBA175 0.05 (0.02–0.07) P < .001; PfMSP2 0.02 (0.003–0.04), P = .025; PfMSP3 0.018 (−0.001 to 0.04), P = .063; PvAMA1 − 0.0004 (−0.01 to 0.01), P = .96; measles −0.003 (−0.015 to 0.01), P = .63.

Mentions: Descriptive univariable analysis suggested that case subjects began pregnancy with higher levels of antibodies, compared with control subjects (Figure 1). Mixed-effect linear models showed that the greater fluctuating antibody responses observed in case subjects was associated with the maintenance of antibody levels at significantly higher mean levels, compared with control subjects or case subjects infected with a Plasmodium species different to the species of the antibody response; mean antibody levels were 0.08 (PvAMA1) to 0.58 (PfAMA1) higher in species-specific case subjects than in uninfected control low schizont lysate responders (P < .0001) (Table 2). Case subjects who were infected with P. vivax only (ie, no P. falciparum infection detected) had mean antibody levels against P. falciparum antigens that were comparable to those of uninfected control low schizont lysate responders (P ≥ .142) (Table 2). Associations with gravidity were seen with the antibodies to the pregnancy-specific PfVAR2CSA antigen (mean levels were 0.09 higher in multigravida than in primigravida; P = .018) but variably with merozoite antigens (Table 2). The maintenance of antibody responses in case subjects infected with P. falciparum and P. vivax at significantly higher levels relative to uninfected individuals suggested that concurrent infection has a role in boosting or maintaining antibodies. To confirm this, further linear mixed-effects analyses were conducted in case subjects infected with P. falciparum and P. vivax. This revealed that antibody levels to the pregnancy-specific PfVAR2CSA and P. falciparum merozoite antigens increased with each successive infection (Figure 4, P ≤ .07), providing evidence of antibody boosting, whereas levels of antibodies to P. vivax AMA1 did not (P = .96).Table 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)

Anti–Plasmodium falciparum levels increase with each successive P. falciparum infection. Multivariable linear mixed-effects modeling of the association between antibody levels and number of episodes in species-specific cases (n = 94 and n = 83 for P. falciparum and P. vivax analysis, respectively). The coefficients (95% confidence interval [CI]) for the estimated mean increase in antibody levels per increase in P. falciparum episode number were as follows: PfVAR2CSA 0.03 (0.01–0.05), P = .011; PfAMA1 0.05 (0.02–0.08), P < .001; PfEBA175 0.05 (0.02–0.07) P < .001; PfMSP2 0.02 (0.003–0.04), P = .025; PfMSP3 0.018 (−0.001 to 0.04), P = .063; PvAMA1 − 0.0004 (−0.01 to 0.01), P = .96; measles −0.003 (−0.015 to 0.01), P = .63.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

JIS566F4: Anti–Plasmodium falciparum levels increase with each successive P. falciparum infection. Multivariable linear mixed-effects modeling of the association between antibody levels and number of episodes in species-specific cases (n = 94 and n = 83 for P. falciparum and P. vivax analysis, respectively). The coefficients (95% confidence interval [CI]) for the estimated mean increase in antibody levels per increase in P. falciparum episode number were as follows: PfVAR2CSA 0.03 (0.01–0.05), P = .011; PfAMA1 0.05 (0.02–0.08), P < .001; PfEBA175 0.05 (0.02–0.07) P < .001; PfMSP2 0.02 (0.003–0.04), P = .025; PfMSP3 0.018 (−0.001 to 0.04), P = .063; PvAMA1 − 0.0004 (−0.01 to 0.01), P = .96; measles −0.003 (−0.015 to 0.01), P = .63.
Mentions: Descriptive univariable analysis suggested that case subjects began pregnancy with higher levels of antibodies, compared with control subjects (Figure 1). Mixed-effect linear models showed that the greater fluctuating antibody responses observed in case subjects was associated with the maintenance of antibody levels at significantly higher mean levels, compared with control subjects or case subjects infected with a Plasmodium species different to the species of the antibody response; mean antibody levels were 0.08 (PvAMA1) to 0.58 (PfAMA1) higher in species-specific case subjects than in uninfected control low schizont lysate responders (P < .0001) (Table 2). Case subjects who were infected with P. vivax only (ie, no P. falciparum infection detected) had mean antibody levels against P. falciparum antigens that were comparable to those of uninfected control low schizont lysate responders (P ≥ .142) (Table 2). Associations with gravidity were seen with the antibodies to the pregnancy-specific PfVAR2CSA antigen (mean levels were 0.09 higher in multigravida than in primigravida; P = .018) but variably with merozoite antigens (Table 2). The maintenance of antibody responses in case subjects infected with P. falciparum and P. vivax at significantly higher levels relative to uninfected individuals suggested that concurrent infection has a role in boosting or maintaining antibodies. To confirm this, further linear mixed-effects analyses were conducted in case subjects infected with P. falciparum and P. vivax. This revealed that antibody levels to the pregnancy-specific PfVAR2CSA and P. falciparum merozoite antigens increased with each successive infection (Figure 4, P ≤ .07), providing evidence of antibody boosting, whereas levels of antibodies to P. vivax AMA1 did not (P = .96).Table 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