Early gamma interferon and interleukin-2 responses to vaccination predict the late resting memory in malaria-naïve and malaria-exposed individuals.
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.
Bejon
Philip
P
Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), P.O. Box 230, Kilifi, Kenya. pbejon@kilifi.mimcom.net
Keating
Sheila
S
Mwacharo
Jedidah
J
Kai
Oscar K
OK
Dunachie
Susanna
S
Walther
Michael
M
Berthoud
Tamara
T
Lang
Trudie
T
Epstein
Judy
J
Carucci
Daniel
D
Moris
Philippe
P
Cohen
Joe
J
Gilbert
Sarah C
SC
Peshu
Norbert
N
Marsh
Kevin
K
Hill
Adrian V S
AV
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
D007376:Interleukin-2; D017780:Malaria Vaccines; D007371:Interferon-gamma