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Infection and Immunity, November 2006, p. 6331-6338, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00774-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Early Gamma Interferon and Interleukin-2 Responses to Vaccination Predict the Late Resting Memory in Malaria-Naïve and Malaria-Exposed Individuals{triangledown}

Philip Bejon,1,2* Sheila Keating,3 Jedidah Mwacharo,1 Oscar K. Kai,1 Susanna Dunachie,2 Michael Walther,2 Tamara Berthoud,2 Trudie Lang,2 Judy Epstein,5 Daniel Carucci,5 Philippe Moris,6 Joe Cohen,6 Sarah C. Gilbert,3 Norbert Peshu,1 Kevin Marsh,1,4 and Adrian V. S. Hill2,3

Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), P.O. Box 230, Kilifi, Kenya,1 Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, OX3 7LJ United Kingdom,2 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN United Kingdom,3 Nuffield Department of Clinical Medicine, Oxford University, John Radcliffe Hospital, Oxford, United Kingdom,4 Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, Maryland,5 GlaxoSmithKline Biologicals, Rixensart, Belgium6

Received 15 May 2006/ Returned for modification 3 July 2006/ Accepted 3 September 2006

Two different cell populations respond to potent T-cell-inducing vaccinations. The induction and loss of effector cells can be seen using an ex vivo enzyme-linked immunospot (ELISPOT) assay, but the more durable resting memory response is demonstrable by a cultured ELISPOT assay. The relationship of the early effector response to durable resting memory is incompletely understood. Effector phenotype is usually identified by gamma interferon (IFN-{gamma}) production, but interleukin-2 (IL-2) has been specifically linked to the differentiation of memory cells. Here, IFN-{gamma}- and IL-2-secreting effector cells were identified by an ex vivo ELISPOT assay 1 week after vaccination and compared with the resting memory responses detected by a cultured ELISPOT assay 3 months later. The different kinetics and induction of IL-2 by different vaccines and natural exposure are described. Furthermore, both early IFN-{gamma} and IL-2 production independently predicted subsequent memory responses at 3 months in malaria-naïve volunteers, but only IFN-{gamma} predicted memory in malaria-exposed volunteers. However, dual ELISPOT assays were also performed on malaria-exposed volunteers to identify cells producing both cytokines simultaneously. This demonstrated that double-cytokine-producing cells were highly predictive of memory. This assay may be useful in predicting vaccinations most likely to generate stable, long-term memory responses.

* Corresponding author. Mailing address: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), P.O. Box 230, Kilifi, Kenya. Phone: 254 415 22063. Fax: 254 415 22396. E-mail: pbejon{at}kilifi.mimcom.net.

{triangledown} Published ahead of print on 11 September 2006.

Editor: J. F. Urban, Jr.

Infection and Immunity, November 2006, p. 6331-6338, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00774-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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