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Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children.

Bejon P, Cook J, Bergmann-Leitner E, Olotu A, Lusingu J, Mwacharo J, Vekemans J, Njuguna P, Leach A, Lievens M, Dutta S, von Seidlein L, Savarese B, Villafana T, Lemnge MM, Cohen J, Marsh K, Corran PH, Angov E, Riley EM, Drakeley CJ - J. Infect. Dis. (2011)

Bottom Line: Anti-MSP-3 antibody concentrations gradually increased, and GIA gradually decreased up to 32 months.Vaccination with RTS,S/AS01(E) resulted in modest reductions in AMA-1, EBA-175, MSP-1(42), and MSP-3 antibody concentrations and no significant change in GIA.Vaccination with RTS,S/AS01E reduces exposure to blood-stage parasites and, thus, reduces anti-merozoite antigen antibody concentrations.

View Article: PubMed Central - PubMed

Affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Kilifi, Kenya. pbejon@kilifi.kemri-wellcome.org

ABSTRACT

Background: RTS,S/AS01(E) is the lead candidate malaria vaccine and confers pre-erythrocytic immunity. Vaccination may therefore impact acquired immunity to blood-stage malaria parasites after natural infection.

Methods: We measured, by enzyme-linked immunosorbent assay, antibodies to 4 Plasmodium falciparum merozoite antigens (AMA-1, MSP-1(42), EBA-175, and MSP-3) and by growth inhibitory activity (GIA) using 2 parasite clones (FV0 and 3D7) at 4 times on 860 children who were randomized to receive with RTS,S/AS01(E) or a control vaccine.

Results:  Antibody concentrations to AMA-1, EBA-175, and MSP-1(42) decreased with age during the first year of life, then increased to 32 months of age. Anti-MSP-3 antibody concentrations gradually increased, and GIA gradually decreased up to 32 months. Vaccination with RTS,S/AS01(E) resulted in modest reductions in AMA-1, EBA-175, MSP-1(42), and MSP-3 antibody concentrations and no significant change in GIA. Increasing anti-merozoite antibody concentrations and GIA were prospectively associated with increased risk of clinical malaria.

Conclusions: Vaccination with RTS,S/AS01E reduces exposure to blood-stage parasites and, thus, reduces anti-merozoite antigen antibody concentrations. However, in this study, these antibodies were not correlates of clinical immunity to malaria. Instead, heterogeneous exposure led to confounded, positive associations between increasing antibody concentration and increasing risk of clinical malaria.

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Related in: MedlinePlus

Maps of participants’ residences, showing the relative AMA-1 antibody concentrations by intensity of shading for the green boxes, relative to the areas with highest intensity of clinical malaria episodes shown by black circles.
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fig3: Maps of participants’ residences, showing the relative AMA-1 antibody concentrations by intensity of shading for the green boxes, relative to the areas with highest intensity of clinical malaria episodes shown by black circles.

Mentions: To test the hypothesis that exposure to malaria infection confounds the analysis by leading to both higher antibody concentrations and ongoing higher risk of future malaria infection, we identified the geographical area with highest incidence of clinical malaria cases among the cohort with use of SaTScan. Antibody concentrations were higher in the high-transmission area (Figure 3). Antibody concentration predicted residence in the high-transmission area for AMA-1 (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.06–1.29; P = .002), EBA-175 (OR, 1.13; 95% CI, 1.03–1.26; P = .015), MSP-142 (OR, 1.22; 95% CI, 1.12–1.34; P < .0005), MSP-3 (OR, 1.22; 95% CI, 1.09–1.36; P <.0005), GIA for 3D7 (OR, 1.13; 95% CI, 1.10–1.18; P < .0005), and GIA for FV0 (OR, 1.30; 95% CI, 1.24–1.37; P < .0005).


Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children.

Bejon P, Cook J, Bergmann-Leitner E, Olotu A, Lusingu J, Mwacharo J, Vekemans J, Njuguna P, Leach A, Lievens M, Dutta S, von Seidlein L, Savarese B, Villafana T, Lemnge MM, Cohen J, Marsh K, Corran PH, Angov E, Riley EM, Drakeley CJ - J. Infect. Dis. (2011)

Maps of participants’ residences, showing the relative AMA-1 antibody concentrations by intensity of shading for the green boxes, relative to the areas with highest intensity of clinical malaria episodes shown by black circles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105039&req=5

fig3: Maps of participants’ residences, showing the relative AMA-1 antibody concentrations by intensity of shading for the green boxes, relative to the areas with highest intensity of clinical malaria episodes shown by black circles.
Mentions: To test the hypothesis that exposure to malaria infection confounds the analysis by leading to both higher antibody concentrations and ongoing higher risk of future malaria infection, we identified the geographical area with highest incidence of clinical malaria cases among the cohort with use of SaTScan. Antibody concentrations were higher in the high-transmission area (Figure 3). Antibody concentration predicted residence in the high-transmission area for AMA-1 (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.06–1.29; P = .002), EBA-175 (OR, 1.13; 95% CI, 1.03–1.26; P = .015), MSP-142 (OR, 1.22; 95% CI, 1.12–1.34; P < .0005), MSP-3 (OR, 1.22; 95% CI, 1.09–1.36; P <.0005), GIA for 3D7 (OR, 1.13; 95% CI, 1.10–1.18; P < .0005), and GIA for FV0 (OR, 1.30; 95% CI, 1.24–1.37; P < .0005).

Bottom Line: Anti-MSP-3 antibody concentrations gradually increased, and GIA gradually decreased up to 32 months.Vaccination with RTS,S/AS01(E) resulted in modest reductions in AMA-1, EBA-175, MSP-1(42), and MSP-3 antibody concentrations and no significant change in GIA.Vaccination with RTS,S/AS01E reduces exposure to blood-stage parasites and, thus, reduces anti-merozoite antigen antibody concentrations.

View Article: PubMed Central - PubMed

Affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Kilifi, Kenya. pbejon@kilifi.kemri-wellcome.org

ABSTRACT

Background: RTS,S/AS01(E) is the lead candidate malaria vaccine and confers pre-erythrocytic immunity. Vaccination may therefore impact acquired immunity to blood-stage malaria parasites after natural infection.

Methods: We measured, by enzyme-linked immunosorbent assay, antibodies to 4 Plasmodium falciparum merozoite antigens (AMA-1, MSP-1(42), EBA-175, and MSP-3) and by growth inhibitory activity (GIA) using 2 parasite clones (FV0 and 3D7) at 4 times on 860 children who were randomized to receive with RTS,S/AS01(E) or a control vaccine.

Results:  Antibody concentrations to AMA-1, EBA-175, and MSP-1(42) decreased with age during the first year of life, then increased to 32 months of age. Anti-MSP-3 antibody concentrations gradually increased, and GIA gradually decreased up to 32 months. Vaccination with RTS,S/AS01(E) resulted in modest reductions in AMA-1, EBA-175, MSP-1(42), and MSP-3 antibody concentrations and no significant change in GIA. Increasing anti-merozoite antibody concentrations and GIA were prospectively associated with increased risk of clinical malaria.

Conclusions: Vaccination with RTS,S/AS01E reduces exposure to blood-stage parasites and, thus, reduces anti-merozoite antigen antibody concentrations. However, in this study, these antibodies were not correlates of clinical immunity to malaria. Instead, heterogeneous exposure led to confounded, positive associations between increasing antibody concentration and increasing risk of clinical malaria.

Show MeSH
Related in: MedlinePlus