Early Gamma Interferon and Interleukin-2 Responses to Vaccination Predict the Late Resting Memory in Malaria-Naïve and Malaria-Exposed Individuals
Bejon P., Keating S., Mwacharo J., Kai OK., Dunachie S., Walther M., Berthoud T., Lang T., Epstein J., Carucci D., Moris P., Cohen J., Gilbert SC., Peshu N., Marsh K., Hill AVS.
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-γ) production, but interleukin-2 (IL-2) has been specifically linked to the differentiation of memory cells. Here, IFN-γ- 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-γ and IL-2 production independently predicted subsequent memory responses at 3 months in malaria-naïve volunteers, but only IFN-γ 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.