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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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A, Scatter plot of age (x axis) against AMA-1 antibody concentration with the fitted fractional polynomial: Concentration=m1*age−0.5 + m2*ln(age), where m refers to coefficients fitted by the regression model. B, Scatter plot of calendar date (x axis) against AMA-1 antibody concentration with the fitted fractional polynomial: Concentration=m1*date−2 + m2*date−2 *ln(date). C, Scatter plot of calendar date (x axis) against GIA for FV0 parasites with the fitted fractional polynomial: Concentration=m1*date−2 + m2*date−2 *ln(date). D, The incidence of clinical malaria per month by calendar month.
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fig1: A, Scatter plot of age (x axis) against AMA-1 antibody concentration with the fitted fractional polynomial: Concentration=m1*age−0.5 + m2*ln(age), where m refers to coefficients fitted by the regression model. B, Scatter plot of calendar date (x axis) against AMA-1 antibody concentration with the fitted fractional polynomial: Concentration=m1*date−2 + m2*date−2 *ln(date). C, Scatter plot of calendar date (x axis) against GIA for FV0 parasites with the fitted fractional polynomial: Concentration=m1*date−2 + m2*date−2 *ln(date). D, The incidence of clinical malaria per month by calendar month.

Mentions: The best-fit fractional polynomials for the age profile of antibody concentrations suggested that, for AMA-1, EBA-175, and MSP-142, antibody concentrations were highest in the youngest children tested, decreased to a nadir just before 1 year of age, and then steadily increased in older children (Table 1, Figure 1a). The best fit for anti–MSP-3 antibody concentrations suggested a simple linear increase in concentrations with increasing age (Table 1). GIA steadily decreased with increasing age (Table 1).


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)

A, Scatter plot of age (x axis) against AMA-1 antibody concentration with the fitted fractional polynomial: Concentration=m1*age−0.5 + m2*ln(age), where m refers to coefficients fitted by the regression model. B, Scatter plot of calendar date (x axis) against AMA-1 antibody concentration with the fitted fractional polynomial: Concentration=m1*date−2 + m2*date−2 *ln(date). C, Scatter plot of calendar date (x axis) against GIA for FV0 parasites with the fitted fractional polynomial: Concentration=m1*date−2 + m2*date−2 *ln(date). D, The incidence of clinical malaria per month by calendar month.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: A, Scatter plot of age (x axis) against AMA-1 antibody concentration with the fitted fractional polynomial: Concentration=m1*age−0.5 + m2*ln(age), where m refers to coefficients fitted by the regression model. B, Scatter plot of calendar date (x axis) against AMA-1 antibody concentration with the fitted fractional polynomial: Concentration=m1*date−2 + m2*date−2 *ln(date). C, Scatter plot of calendar date (x axis) against GIA for FV0 parasites with the fitted fractional polynomial: Concentration=m1*date−2 + m2*date−2 *ln(date). D, The incidence of clinical malaria per month by calendar month.
Mentions: The best-fit fractional polynomials for the age profile of antibody concentrations suggested that, for AMA-1, EBA-175, and MSP-142, antibody concentrations were highest in the youngest children tested, decreased to a nadir just before 1 year of age, and then steadily increased in older children (Table 1, Figure 1a). The best fit for anti–MSP-3 antibody concentrations suggested a simple linear increase in concentrations with increasing age (Table 1). GIA steadily decreased with increasing age (Table 1).

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