title: Early gamma interferon and interleukin-2 responses to vaccination predict the late resting memory in malaria-naïve and malaria-exposed individuals.
abstract: 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.
authors.affiliation: Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), P.O. Box 230, Kilifi, Kenya. pbejon@kilifi.mimcom.net
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Sheila
authors.initials: S
authors.lastname: Keating
authors.forename: Jedidah
authors.initials: J
authors.lastname: Mwacharo
authors.forename: Oscar K
authors.initials: OK
authors.lastname: Kai
authors.forename: Susanna
authors.initials: S
authors.lastname: Dunachie
authors.forename: Michael
authors.initials: M
authors.lastname: Walther
authors.forename: Tamara
authors.initials: T
authors.lastname: Berthoud
authors.forename: Trudie
authors.initials: T
authors.lastname: Lang
authors.forename: Judy
authors.initials: J
authors.lastname: Epstein
authors.forename: Daniel
authors.initials: D
authors.lastname: Carucci
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Norbert
authors.initials: N
authors.lastname: Peshu
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000818:Animals; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008288:Malaria / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D010961:Plasmodium / Q000276:immunology; D011237:Predictive Value of Tests; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D013997:Time Factors
chemical_list: D007376:Interleukin-2; D017780:Malaria Vaccines; D007371:Interferon-gamma