Durable human memory T cells quantifiable by cultured enzyme-linked immunospot assays are induced by heterologous prime boost immunization and correlate with protection against malaria.
Immunological memory is a required component of protective antimalarial responses raised by T cell-inducing vaccines. The magnitude of ex vivo IFN-gamma T cell responses is widely used to identify immunogenic vaccines although this response usually wanes and may disappear within weeks. However, protection in the field is likely to depend on durable central memory T cells that are not detected by this assay. To identify longer-lived memory T cells, PBMC from malaria-naive vaccinated volunteers who had received prime boost vaccinations with a combination of DNA and/or viral vectors encoding the multiepitope string-thrombospondin-related adhesion protein Ag were cultured in vitro with Ag for 10 days before the ELISPOT assay. Ex vivo T cell responses peaked at 7 days after the final immunization and declined substantially over 6 mo, but responses identified after T cell culture increased over the 6-mo period after the final immunization. Moreover, individual cultured ELISPOT responses at the day of challenge time point correlated significantly with degree of protection against malaria sporozoite challenge, whereas ex vivo responses did not, despite a correlation between the peak ex vivo response and magnitude of memory responses 6 mo later. This cultured assay identifies long-lasting protective T cell responses and therefore offers an attractive option for assessments of vaccine immunogenicity.
Keating
Sheila M
SM
Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine, Churchill Hospital, Oxford, United Kingdom.
Bejon
Philip
P
Berthoud
Tamara
T
Vuola
Jenni M
JM
Todryk
Stephen
S
Webster
Daniel P
DP
Dunachie
Susanna J
SJ
Moorthy
Vasee S
VS
McConkey
Samuel J
SJ
Gilbert
Sarah C
SC
Hill
Adrian V S
AV
D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D017780:Malaria Vaccines; D007371:Interferon-gamma