Distinct helper t cell type 1 and 2 responses associated with malaria protection and risk in rts,s/as01e vaccinees

Gemma Moncunill, Maxmillian Mpina, Augusto J. Nhabomba, Ruth Aguilar, Aintzane Ayestaran, Héctor Sanz, Joseph J. Campo, Chenjerai Jairoce, Diana Barrios, Yan Dong, Nuria Díez-Padrisa, José F. Fernandes, Salim Abdulla, Jahit Sacarlal, Nana A. Williams, Jaroslaw Harezlak, Benjamin Mordmüller, Selidji T. Agnandji, John J. Aponte, Claudia Daubenberger & 2 others Clarissa Valim, Carlota Dobaño

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background. The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination. Methods. We performed a matched case-control study nested within the multicenter African RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106 RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization. Crude concentrations and ratios of antigen to background control were analyzed. Results. Interleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E vaccination (adjusted P ≤ .01). IL-5 circumsporozoite protein (CSP) ratios, a helper T cell type 2 cytokine, correlated with higher odds of malaria in RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value adjusted for multiple testing = .03). In multimarker analysis, the helper T cell type 1 (TH1)-related markers interferon-γ, IL-15, and granulocyte-macrophage colony-stimulating factor protected from subsequent malaria, in contrast to IL-5 and RANTES, which increased the odds of malaria. Conclusions. RTS,S/AS01E-induced IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may be involved in protective mechanisms. Efforts to develop second-generation vaccine candidates may concentrate on adjuvants that modulate the immune system to support enhanced TH1 responses and decreased IL-5 responses.

Original languageEnglish (US)
Pages (from-to)746-755
Number of pages10
JournalClinical Infectious Diseases
Volume65
Issue number5
DOIs
StatePublished - 2017

Fingerprint

Helper-Inducer T-Lymphocytes
Malaria
Interleukin-5
Vaccination
Vaccines
Malaria Vaccines
Antigens
Interleukin-15
Chemokine CCL5
Th2 Cells
Th1 Cells
Granulocyte-Macrophage Colony-Stimulating Factor
S Phase
Cellular Immunity
Interferons
Interleukin-2
Case-Control Studies
Immune System
Immunity
Proteins

Keywords

  • Cellular immune responses
  • Cytokines
  • Immunity
  • Malaria
  • Vaccine

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Moncunill, G., Mpina, M., Nhabomba, A. J., Aguilar, R., Ayestaran, A., Sanz, H., ... Dobaño, C. (2017). Distinct helper t cell type 1 and 2 responses associated with malaria protection and risk in rts,s/as01e vaccinees. Clinical Infectious Diseases, 65(5), 746-755. https://doi.org/10.1093/cid/cix429

Distinct helper t cell type 1 and 2 responses associated with malaria protection and risk in rts,s/as01e vaccinees. / Moncunill, Gemma; Mpina, Maxmillian; Nhabomba, Augusto J.; Aguilar, Ruth; Ayestaran, Aintzane; Sanz, Héctor; Campo, Joseph J.; Jairoce, Chenjerai; Barrios, Diana; Dong, Yan; Díez-Padrisa, Nuria; Fernandes, José F.; Abdulla, Salim; Sacarlal, Jahit; Williams, Nana A.; Harezlak, Jaroslaw; Mordmüller, Benjamin; Agnandji, Selidji T.; Aponte, John J.; Daubenberger, Claudia; Valim, Clarissa; Dobaño, Carlota.

In: Clinical Infectious Diseases, Vol. 65, No. 5, 2017, p. 746-755.

Research output: Contribution to journalArticle

Moncunill, G, Mpina, M, Nhabomba, AJ, Aguilar, R, Ayestaran, A, Sanz, H, Campo, JJ, Jairoce, C, Barrios, D, Dong, Y, Díez-Padrisa, N, Fernandes, JF, Abdulla, S, Sacarlal, J, Williams, NA, Harezlak, J, Mordmüller, B, Agnandji, ST, Aponte, JJ, Daubenberger, C, Valim, C & Dobaño, C 2017, 'Distinct helper t cell type 1 and 2 responses associated with malaria protection and risk in rts,s/as01e vaccinees', Clinical Infectious Diseases, vol. 65, no. 5, pp. 746-755. https://doi.org/10.1093/cid/cix429
Moncunill, Gemma ; Mpina, Maxmillian ; Nhabomba, Augusto J. ; Aguilar, Ruth ; Ayestaran, Aintzane ; Sanz, Héctor ; Campo, Joseph J. ; Jairoce, Chenjerai ; Barrios, Diana ; Dong, Yan ; Díez-Padrisa, Nuria ; Fernandes, José F. ; Abdulla, Salim ; Sacarlal, Jahit ; Williams, Nana A. ; Harezlak, Jaroslaw ; Mordmüller, Benjamin ; Agnandji, Selidji T. ; Aponte, John J. ; Daubenberger, Claudia ; Valim, Clarissa ; Dobaño, Carlota. / Distinct helper t cell type 1 and 2 responses associated with malaria protection and risk in rts,s/as01e vaccinees. In: Clinical Infectious Diseases. 2017 ; Vol. 65, No. 5. pp. 746-755.
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abstract = "Background. The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination. Methods. We performed a matched case-control study nested within the multicenter African RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106 RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization. Crude concentrations and ratios of antigen to background control were analyzed. Results. Interleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E vaccination (adjusted P ≤ .01). IL-5 circumsporozoite protein (CSP) ratios, a helper T cell type 2 cytokine, correlated with higher odds of malaria in RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10{\%} increases of CSP ratios; P value adjusted for multiple testing = .03). In multimarker analysis, the helper T cell type 1 (TH1)-related markers interferon-γ, IL-15, and granulocyte-macrophage colony-stimulating factor protected from subsequent malaria, in contrast to IL-5 and RANTES, which increased the odds of malaria. Conclusions. RTS,S/AS01E-induced IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may be involved in protective mechanisms. Efforts to develop second-generation vaccine candidates may concentrate on adjuvants that modulate the immune system to support enhanced TH1 responses and decreased IL-5 responses.",
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T1 - Distinct helper t cell type 1 and 2 responses associated with malaria protection and risk in rts,s/as01e vaccinees

AU - Moncunill, Gemma

AU - Mpina, Maxmillian

AU - Nhabomba, Augusto J.

AU - Aguilar, Ruth

AU - Ayestaran, Aintzane

AU - Sanz, Héctor

AU - Campo, Joseph J.

AU - Jairoce, Chenjerai

AU - Barrios, Diana

AU - Dong, Yan

AU - Díez-Padrisa, Nuria

AU - Fernandes, José F.

AU - Abdulla, Salim

AU - Sacarlal, Jahit

AU - Williams, Nana A.

AU - Harezlak, Jaroslaw

AU - Mordmüller, Benjamin

AU - Agnandji, Selidji T.

AU - Aponte, John J.

AU - Daubenberger, Claudia

AU - Valim, Clarissa

AU - Dobaño, Carlota

PY - 2017

Y1 - 2017

N2 - Background. The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination. Methods. We performed a matched case-control study nested within the multicenter African RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106 RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization. Crude concentrations and ratios of antigen to background control were analyzed. Results. Interleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E vaccination (adjusted P ≤ .01). IL-5 circumsporozoite protein (CSP) ratios, a helper T cell type 2 cytokine, correlated with higher odds of malaria in RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value adjusted for multiple testing = .03). In multimarker analysis, the helper T cell type 1 (TH1)-related markers interferon-γ, IL-15, and granulocyte-macrophage colony-stimulating factor protected from subsequent malaria, in contrast to IL-5 and RANTES, which increased the odds of malaria. Conclusions. RTS,S/AS01E-induced IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may be involved in protective mechanisms. Efforts to develop second-generation vaccine candidates may concentrate on adjuvants that modulate the immune system to support enhanced TH1 responses and decreased IL-5 responses.

AB - Background. The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination. Methods. We performed a matched case-control study nested within the multicenter African RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106 RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization. Crude concentrations and ratios of antigen to background control were analyzed. Results. Interleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E vaccination (adjusted P ≤ .01). IL-5 circumsporozoite protein (CSP) ratios, a helper T cell type 2 cytokine, correlated with higher odds of malaria in RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value adjusted for multiple testing = .03). In multimarker analysis, the helper T cell type 1 (TH1)-related markers interferon-γ, IL-15, and granulocyte-macrophage colony-stimulating factor protected from subsequent malaria, in contrast to IL-5 and RANTES, which increased the odds of malaria. Conclusions. RTS,S/AS01E-induced IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may be involved in protective mechanisms. Efforts to develop second-generation vaccine candidates may concentrate on adjuvants that modulate the immune system to support enhanced TH1 responses and decreased IL-5 responses.

KW - Cellular immune responses

KW - Cytokines

KW - Immunity

KW - Malaria

KW - Vaccine

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DO - 10.1093/cid/cix429

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