Effect of the Pre-erythrocytic candidate malaria vaccine RTS,S/AS01e on blood stage immunity in young children.

Phillip 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 Lemnge; Joe Cohen; Kevin Marsh; Patrick Corran; Evelina Angov; Eleanor Riley; Chris Drakeley

doi:10.1093/infdis/jir222

Effect of the Pre-erythrocytic candidate malaria vaccine RTS,S/AS01e on blood stage immunity in young children.

Phillip 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 Lemnge, Joe Cohen, Kevin Marsh, Patrick Corran, Evelina Angov, Eleanor RileyChris Drakeley

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	9-18
Number of pages	10
Journal	Journal of Infectious Diseases
Volume	204
Issue number	1
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., Cohen, J., Marsh, K., Corran, P., Angov, E., ... Drakeley, C. (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

@article{7dcfc125efa74254b218088ca9fdb563,

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.",

keywords = "apical membrane antigen 1, EBA 175, malaria vaccine, merozoite surface protein 1, merozoite surface protein 3, parasite antigen, unclassified drug, age distribution, antibody blood level, article, controlled study, disease transmission, drug efficacy, drug safety, enzyme linked immunosorbent assay, growth inhibition, human, immunity, infection risk, major clinical study, malaria, malaria control, multiple cycle treatment, priority journal, randomized controlled trial, vaccination, Antibodies, Protozoan, Child, Preschool, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Humans, Infant, Longitudinal Studies, Malaria Vaccines, Malaria, Falciparum, Plasmodium falciparum, Protozoan Proteins, Risk Factors",

author = "Phillip 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 Martha Lemnge and Joe Cohen and Kevin Marsh and Patrick Corran and Evelina Angov and Eleanor Riley and Chris Drakeley",

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",

publisher = "Oxford University Press",

number = "1",

}

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, Cohen, J, Marsh, K, Corran, P, Angov, E, Riley, E & Drakeley, C 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

TY - JOUR

T1 - Effect of the Pre-erythrocytic candidate malaria vaccine RTS,S/AS01e on blood stage immunity in young children.

AU - Bejon, Phillip

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

AU - Cohen, Joe

AU - Marsh, Kevin

AU - Corran, Patrick

AU - Angov, Evelina

AU - Riley, Eleanor

AU - Drakeley, Chris

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.

KW - apical membrane antigen 1

KW - EBA 175

KW - malaria vaccine

KW - merozoite surface protein 1

KW - merozoite surface protein 3

KW - parasite antigen

KW - unclassified drug

KW - age distribution

KW - antibody blood level

KW - article

KW - controlled study

KW - disease transmission

KW - drug efficacy

KW - drug safety

KW - enzyme linked immunosorbent assay

KW - growth inhibition

KW - human

KW - immunity

KW - infection risk

KW - major clinical study

KW - malaria

KW - malaria control

KW - multiple cycle treatment

KW - priority journal

KW - randomized controlled trial

KW - vaccination

KW - Antibodies, Protozoan

KW - Child, Preschool

KW - Cohort Studies

KW - Enzyme-Linked Immunosorbent Assay

KW - Humans

KW - Infant

KW - Longitudinal Studies

KW - Malaria Vaccines

KW - Malaria, Falciparum

KW - Plasmodium falciparum

KW - Protozoan Proteins

KW - Risk Factors

U2 - 10.1093/infdis/jir222

DO - 10.1093/infdis/jir222

M3 - Article

VL - 204

SP - 9

EP - 18

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

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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