Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants

Carly M. Bliss; Abdoulie Drammeh; Georgina Bowyer; Guillaume S. Sanou; Ya Jankey Jagne; Oumarou Ouedraogo; Nick J. Edwards; Casimir Tarama; Nicolas Ouedraogo; Mireille Ouedraogo; Jainaba Njie-Jobe; Amidou Diarra; Muhammed O. Afolabi; Alfred B. Tiono; Jean Baptiste Yaro; Uche J. Adetifa; Susanne H. Hodgson; Nicholas A. Anagnostou; Rachel Roberts; Christopher J.A. Duncan; Riccardo Cortese; Nicola K. Viebig; Odile Leroy; Alison M. Lawrie; Katie L. Flanagan; Beate Kampmann; Egeruan B. Imoukhuede; Sodiomon B. Sirima; Kalifa Bojang; Adrian V.S. Hill; Issa Nébié; Katie J. Ewer

doi:10.1016/j.ymthe.2016.11.003

Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants

Carly M. Bliss, Abdoulie Drammeh, Georgina Bowyer, Guillaume S. Sanou, Ya Jankey Jagne, Oumarou Ouedraogo, Nick J. Edwards, Casimir Tarama, Nicolas Ouedraogo, Mireille Ouedraogo, Jainaba Njie-Jobe, Amidou Diarra, Muhammed O. Afolabi, Alfred B. Tiono, Jean Baptiste Yaro, Uche J. Adetifa, Susanne H. Hodgson, Nicholas A. Anagnostou, Rachel Roberts, Christopher J.A. DuncanRiccardo Cortese, Nicola K. Viebig, Odile Leroy, Alison M. Lawrie, Katie L. Flanagan, Beate Kampmann, Egeruan B. Imoukhuede, Sodiomon B. Sirima, Kalifa Bojang, Adrian V.S. Hill, Issa Nébié, Katie J. Ewer

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

36 Scopus citations

Abstract

Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8⁺ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8⁺ and CD4⁺ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine.

Original language	English
Pages (from-to)	547-559
Number of pages	13
Journal	Molecular Therapy
Volume	25
Issue number	2
DOIs	https://doi.org/10.1016/j.ymthe.2016.11.003
State	Published - 1 Feb 2017
Externally published	Yes

Keywords

Phase I trial
T cells
antibodies
malaria
vaccine
viral vectors

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10.1016/j.ymthe.2016.11.003

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Bliss, C. M., Drammeh, A., Bowyer, G., Sanou, G. S., Jagne, Y. J., Ouedraogo, O., Edwards, N. J., Tarama, C., Ouedraogo, N., Ouedraogo, M., Njie-Jobe, J., Diarra, A., Afolabi, M. O., Tiono, A. B., Yaro, J. B., Adetifa, U. J., Hodgson, S. H., Anagnostou, N. A., Roberts, R., ... Ewer, K. J. (2017). Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants. Molecular Therapy, 25(2), 547-559. https://doi.org/10.1016/j.ymthe.2016.11.003

@article{daf7b384a5b2495998c1a2faac4e587b,

title = "Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants",

abstract = "Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine.",

keywords = "Phase I trial, T cells, antibodies, malaria, vaccine, viral vectors",

author = "Bliss, {Carly M.} and Abdoulie Drammeh and Georgina Bowyer and Sanou, {Guillaume S.} and Jagne, {Ya Jankey} and Oumarou Ouedraogo and Edwards, {Nick J.} and Casimir Tarama and Nicolas Ouedraogo and Mireille Ouedraogo and Jainaba Njie-Jobe and Amidou Diarra and Afolabi, {Muhammed O.} and Tiono, {Alfred B.} and Yaro, {Jean Baptiste} and Adetifa, {Uche J.} and Hodgson, {Susanne H.} and Anagnostou, {Nicholas A.} and Rachel Roberts and Duncan, {Christopher J.A.} and Riccardo Cortese and Viebig, {Nicola K.} and Odile Leroy and Lawrie, {Alison M.} and Flanagan, {Katie L.} and Beate Kampmann and Imoukhuede, {Egeruan B.} and Sirima, {Sodiomon B.} and Kalifa Bojang and Hill, {Adrian V.S.} and Issa N{\'e}bi{\'e} and Ewer, {Katie J.}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s)",

year = "2017",

month = feb,

day = "1",

doi = "10.1016/j.ymthe.2016.11.003",

language = "English",

volume = "25",

pages = "547--559",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Cell Press",

number = "2",

}

Bliss, CM, Drammeh, A, Bowyer, G, Sanou, GS, Jagne, YJ, Ouedraogo, O, Edwards, NJ, Tarama, C, Ouedraogo, N, Ouedraogo, M, Njie-Jobe, J, Diarra, A, Afolabi, MO, Tiono, AB, Yaro, JB, Adetifa, UJ, Hodgson, SH, Anagnostou, NA, Roberts, R, Duncan, CJA, Cortese, R, Viebig, NK, Leroy, O, Lawrie, AM, Flanagan, KL, Kampmann, B, Imoukhuede, EB, Sirima, SB, Bojang, K, Hill, AVS, Nébié, I & Ewer, KJ 2017, 'Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants', Molecular Therapy, vol. 25, no. 2, pp. 547-559. https://doi.org/10.1016/j.ymthe.2016.11.003

TY - JOUR

T1 - Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants

AU - Bliss, Carly M.

AU - Drammeh, Abdoulie

AU - Bowyer, Georgina

AU - Sanou, Guillaume S.

AU - Jagne, Ya Jankey

AU - Ouedraogo, Oumarou

AU - Edwards, Nick J.

AU - Tarama, Casimir

AU - Ouedraogo, Nicolas

AU - Ouedraogo, Mireille

AU - Njie-Jobe, Jainaba

AU - Diarra, Amidou

AU - Afolabi, Muhammed O.

AU - Tiono, Alfred B.

AU - Yaro, Jean Baptiste

AU - Adetifa, Uche J.

AU - Hodgson, Susanne H.

AU - Anagnostou, Nicholas A.

AU - Roberts, Rachel

AU - Duncan, Christopher J.A.

AU - Cortese, Riccardo

AU - Viebig, Nicola K.

AU - Leroy, Odile

AU - Lawrie, Alison M.

AU - Flanagan, Katie L.

AU - Kampmann, Beate

AU - Imoukhuede, Egeruan B.

AU - Sirima, Sodiomon B.

AU - Bojang, Kalifa

AU - Hill, Adrian V.S.

AU - Nébié, Issa

AU - Ewer, Katie J.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine.

AB - Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine.

KW - Phase I trial

KW - T cells

KW - antibodies

KW - malaria

KW - vaccine

KW - viral vectors

UR - http://www.scopus.com/inward/record.url?scp=85016326575&partnerID=8YFLogxK

U2 - 10.1016/j.ymthe.2016.11.003

DO - 10.1016/j.ymthe.2016.11.003

M3 - Article

C2 - 28153101

AN - SCOPUS:85016326575

SN - 1525-0016

VL - 25

SP - 547

EP - 559

JO - Molecular Therapy

JF - Molecular Therapy

IS - 2

ER -

Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants

Abstract

Keywords

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