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

Philip Bejon; Jackie Cook; Elke Bergmann-Leitner; Ally Olotu; John Lusingu; Jedidah Mwacharo; Johan Vekemans; Patricia Njuguna; Amanda Leach; Marc Lievens; Sheetij Dutta; Lorenz von Seidlein; Barbara Savarese; Tonya Villafana; Martha M Lemnge; Joe Cohen; Kevin Marsh; Patrick H Corran; Evelina Angov; Eleanor M Riley; Chris J Drakeley

doi:10.1093/infdis/jir222

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

Philip Bejon, Jackie Cook, Elke Bergmann-Leitner, Ally Olotu, John Lusingu, Jedidah Mwacharo, Johan Vekemans, Patricia Njuguna, Amanda Leach, Marc Lievens, Sheetij Dutta, Lorenz von Seidlein, Barbara Savarese, Tonya Villafana, Martha M Lemnge, Joe Cohen, Kevin Marsh, Patrick H Corran, Evelina Angov, Eleanor M RileyChris J Drakeley

Centre for Medical Parasitology

40 Citations (Scopus)

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-1₄₂, 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-1₄₂ 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-1₄₂, 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 antimerozoite 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.

Original language	English
Journal	Journal of Infectious Diseases
Volume	204
Issue number	1
Pages (from-to)	9-18
Number of pages	10
ISSN	0022-1899
DOIs	https://doi.org/10.1093/infdis/jir222
Publication status	Published - 1 Jul 2011

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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, M. M., Cohen, J., Marsh, K., Corran, P. H., Angov, E., ... Drakeley, C. J. (2011). Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children. Journal of Infectious Diseases, 204(1), 9-18. https://doi.org/10.1093/infdis/jir222

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 2011, 'Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children', Journal of Infectious Diseases, vol. 204, no. 1, pp. 9-18. https://doi.org/10.1093/infdis/jir222

@article{26fc16f752cd4aac88c1e47bdbed2072,

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

abstract = "Background. RTS,S/AS01E 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-142, 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-142 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/AS01E resulted in modest reductions in AMA-1, EBA-175, MSP-142, 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 antimerozoite 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.",

author = "Philip Bejon and Jackie Cook and Elke Bergmann-Leitner and Ally Olotu and John Lusingu and Jedidah Mwacharo and Johan Vekemans and Patricia Njuguna and Amanda Leach and Marc Lievens and Sheetij Dutta and {von Seidlein}, Lorenz and Barbara Savarese and Tonya Villafana and Lemnge, {Martha M} and Joe Cohen and Kevin Marsh and Corran, {Patrick H} and Evelina Angov and Riley, {Eleanor M} and Drakeley, {Chris J}",

year = "2011",

month = jul,

day = "1",

doi = "10.1093/infdis/jir222",

language = "English",

volume = "204",

pages = "9--18",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

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TY - JOUR

T1 - Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children

AU - Bejon, Philip

AU - Cook, Jackie

AU - Bergmann-Leitner, Elke

AU - Olotu, Ally

AU - Lusingu, John

AU - Mwacharo, Jedidah

AU - Vekemans, Johan

AU - Njuguna, Patricia

AU - Leach, Amanda

AU - Lievens, Marc

AU - Dutta, Sheetij

AU - von Seidlein, Lorenz

AU - Savarese, Barbara

AU - Villafana, Tonya

AU - Lemnge, Martha M

AU - Cohen, Joe

AU - Marsh, Kevin

AU - Corran, Patrick H

AU - Angov, Evelina

AU - Riley, Eleanor M

AU - Drakeley, Chris J

PY - 2011/7/1

Y1 - 2011/7/1

N2 - Background. RTS,S/AS01E 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-142, 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-142 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/AS01E resulted in modest reductions in AMA-1, EBA-175, MSP-142, 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 antimerozoite 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.

AB - Background. RTS,S/AS01E 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-142, 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-142 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/AS01E resulted in modest reductions in AMA-1, EBA-175, MSP-142, 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 antimerozoite 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.

U2 - 10.1093/infdis/jir222

DO - 10.1093/infdis/jir222

M3 - Journal article

C2 - 21628653

SN - 0022-1899

VL - 204

SP - 9

EP - 18

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 1

ER -

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

Abstract

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