This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00774-06v1 74/11/6331    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bejon, P. Articles by Hill, A. V. S. Search for Related Content PubMed PubMed Citation Articles by Bejon, P. Articles by Hill, A. V. S.

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

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-) production, but interleukin-2 (IL-2) has been specifically linked to the differentiation of memory cells. Here, IFN-- 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- and IL-2 production independently predicted subsequent memory responses at 3 months in malaria-naïve volunteers, but only IFN- 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.

Published ahead of print on 11 September 2006.

Editor: J. F. Urban, Jr.

This article has been cited by other articles:

• Huaman, M. C., Martin, L. B., Malkin, E., Narum, D. L., Miller, L. H., Mahanty, S., Long, C. A. (2008). Ex Vivo Cytokine and Memory T Cell Responses to the 42-kDa Fragment of Plasmodium falciparum Merozoite Surface Protein-1 in Vaccinated Volunteers. J. Immunol. 180: 1451-1461 [Abstract] [Full Text]  
• Pichyangkul, S., Kum-Arb, U., Yongvanitchit, K., Limsalakpetch, A., Gettayacamin, M., Lanar, D. E., Ware, L. A., Stewart, V. A., Heppner, D. G., Mettens, P., Cohen, J. D., Ballou, W. R., Fukuda, M. M. (2008). Preclinical Evaluation of the Safety and Immunogenicity of a Vaccine Consisting of Plasmodium falciparum Liver-Stage Antigen 1 with Adjuvant AS01B Administered Alone or Concurrently with the RTS,S/AS01B Vaccine in Rhesus Primates. Infect. Immun. 76: 229-238 [Abstract] [Full Text]  
• Bejon, P., Mwacharo, J., Kai, O., Todryk, S., Keating, S., Lowe, B., Lang, T., Mwangi, T. W., Gilbert, S. C., Peshu, N., Marsh, K., Hill, A. V. S. (2007). The Induction and Persistence of T Cell IFN-{gamma} Responses after Vaccination or Natural Exposure Is Suppressed by Plasmodium falciparum. J. Immunol. 179: 4193-4201 [Abstract] [Full Text]  
• Kim, K. H., Greenfield, W., Shotts, E., Nakagawa, M. (2007). Detection of Human Papillomavirus Type 16-Specific T Lymphocytes by a Recombinant Vaccinia Virus-Based Enzyme-Linked Immunospot Assay. CVI 14: 362-368 [Abstract] [Full Text]