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Distinct helper T cell type 1 and 2 responses associated with malaria protection and risk in RTS,S/AS01E vaccinees

Moncunill, G. and Mpina, M. and Nhabomba, A. J. and Aguilar, R. and Ayestaran, A. and Sanz, H. and Campo, J. J. and Jairoce, C. and Barrios, D. and Dong, Y. and Diez-Padrisa, N. and Fernandes, J. F. and Sacarlal, J. and Williams, N. A. and Harezlak, J. and Mordmuller, B. and Agnandji, S. T. and Aponte, J. J. and Daubenberger, C. and Valim, C. and Dobano, 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). 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Clinical Immunology (Daubenberger)
UniBasel Contributors:Daubenberger, Claudia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:1058-4838
e-ISSN:1537-6591
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:25 Oct 2017 09:54
Deposited On:20 Oct 2017 09:09

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