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 DaubenbergerClarissa Valim, Carlota Dobaño

Research output: Contribution to journalArticle

11 Scopus citations

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 - Jan 1 2017

Keywords

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

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Moncunill, G., Mpina, M., Nhabomba, A. J., Aguilar, R., Ayestaran, A., Sanz, H., Campo, J. J., Jairoce, C., Barrios, D., Dong, Y., Díez-Padrisa, N., Fernandes, J. F., Abdulla, S., Sacarlal, J., Williams, N. A., Harezlak, J., Mordmüller, B., Agnandji, S. T., Aponte, J. J., ... 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