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 Olanrewaju Afolabi, Alfred B. Tiono, Jean Baptiste Yaro, Uche J. Adetifa, Susanne H Hodgson, Nicholas A Anagnostou, Rachel Roberts, Christopher J A Duncan & 12 others Riccardo Cortese, Nicola K Viebig, Odile Leroy, Alison M Lawrie, Katie L. Flanagan, Beate Kampmann, Egeruan Babatunde Imoukhuede, Sodiomon B. Sirima, Kalifa Abubakr Bojang, Adrian V S Hill, Issa Nébié, Katie J Ewer

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10 Citations (Scopus)

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 languageEnglish
Pages (from-to)547-559
Number of pages13
JournalMolecular Therapy
Volume25
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

Keywords

  • antibodies
  • malaria
  • Phase I trial
  • T cells
  • vaccine
  • viral vectors

Cite this

Bliss, C. M., Drammeh, A., Bowyer, G., Sanou, G. S., Jagne, Y. J., Ouedraogo, O., ... 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
Bliss, Carly M ; Drammeh, Abdoulie ; Bowyer, Georgina ; Sanou, Guillaume S. ; Jagne, Ya Jankey ; Ouedraogo, Oumarou ; Edwards, Nick J. ; Tarama, Casimir ; Ouedraogo, Nicolas ; Ouedraogo, Mireille ; Njie-jobe, Jainaba ; Diarra, Amidou ; Afolabi, Muhammed Olanrewaju ; Tiono, Alfred B. ; Yaro, Jean Baptiste ; Adetifa, Uche J. ; Hodgson, Susanne H ; Anagnostou, Nicholas A ; Roberts, Rachel ; Duncan, Christopher J A ; Cortese, Riccardo ; Viebig, Nicola K ; Leroy, Odile ; Lawrie, Alison M ; Flanagan, Katie L. ; Kampmann, Beate ; Imoukhuede, Egeruan Babatunde ; Sirima, Sodiomon B. ; Bojang, Kalifa Abubakr ; Hill, Adrian V S ; Nébié, Issa ; Ewer, Katie J. / Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants. In: Molecular Therapy. 2017 ; Vol. 25, No. 2. pp. 547-559.
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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.",
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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, KA, 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

Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants. / Bliss, Carly M; Drammeh, Abdoulie; Bowyer, Georgina; Sanou, Guillaume S.; Jagne, Ya Jankey; Ouedraogo, Oumarou; Edwards, Nick J.; Tarama, Casimir; Ouedraogo, Nicolas; Ouedraogo, Mireille; Njie-jobe, Jainaba; Diarra, Amidou; Afolabi, Muhammed Olanrewaju; Tiono, Alfred B.; Yaro, Jean Baptiste; Adetifa, Uche J.; Hodgson, Susanne H; Anagnostou, Nicholas A; Roberts, Rachel; Duncan, Christopher J A; Cortese, Riccardo; Viebig, Nicola K; Leroy, Odile; Lawrie, Alison M; Flanagan, Katie L.; Kampmann, Beate; Imoukhuede, Egeruan Babatunde; Sirima, Sodiomon B.; Bojang, Kalifa Abubakr; Hill, Adrian V S; Nébié, Issa; Ewer, Katie J.

In: Molecular Therapy, Vol. 25, No. 2, 01.02.2017, p. 547-559.

Research output: Contribution to journalArticleResearchpeer-review

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 Olanrewaju

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 Babatunde

AU - Sirima, Sodiomon B.

AU - Bojang, Kalifa Abubakr

AU - Hill, Adrian V S

AU - Nébié, Issa

AU - Ewer, Katie J

PY - 2017/2/1

Y1 - 2017/2/1

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KW - malaria

KW - Phase I trial

KW - T cells

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KW - viral vectors

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