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, prot...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2005-11, Vol.175 (9), p.5675-5680
Main Authors: Keating, Sheila M, Bejon, Philip, Berthoud, Tamara, Vuola, Jenni M, Todryk, Stephen, Webster, Daniel P, Dunachie, Susanna J, Moorthy, Vasee S, McConkey, Samuel J, Gilbert, Sarah C, Hill, Adrian V. S
Format: Article
Language:English
Subjects:
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Humans
Immunization, Secondary
Immunologic Memory
Interferon-gamma - biosynthesis
Lymphocyte Activation
Malaria - prevention & control
Malaria Vaccines - immunology
T-Lymphocytes - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.175.9.5675