Pushing the frontiers of T-cell vaccines: accurate measurement of human T-cell responses

Expert Rev Vaccines. 2012 Dec;11(12):1459-70. doi: 10.1586/erv.12.125.

Abstract

There is a need for novel approaches to tackle major vaccine challenges such as malaria, tuberculosis and HIV, among others. Success will require vaccines able to induce a cytotoxic T-cell response--a deficiency of most current vaccine approaches. The successful development of T-cell vaccines faces many hurdles, not least being the lack of consensus on a standardized T-cell assay format able to be used as a correlate of vaccine efficacy. Hence, there remains a need for reproducible measures of T-cell immunity proven in human clinical trials to correlate with vaccine protection. The T-cell equivalent of a neutralizing antibody assay would greatly accelerate the development and commercialization of T-cell vaccines. Recent advances have seen a plethora of new T-cell assays become available, including some like cytometry by time-of-flight with extreme multiparameter T-cell phenotyping capability. However, whether it is historic thymidine-based proliferation assays or sophisticated new cytometry assays, each assay has its relative advantages and disadvantages, and relatively few of these assays have yet to be validated in large-scale human vaccine trials. This review examines the current range of T-cell assays and assesses their suitability for use in human vaccine trials. Should one or more of these assays be accepted as an agreed surrogate of T-cell protection by a regulatory agency, this would significantly accelerate the development of T-cell vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Proliferation
  • Clinical Trials as Topic
  • Cytokines / immunology
  • Enzyme-Linked Immunospot Assay
  • Flow Cytometry
  • Humans
  • Immunity, Cellular*
  • Immunoassay / methods*
  • Immunologic Memory
  • Immunophenotyping
  • Leukocytes, Mononuclear / immunology
  • Reproducibility of Results
  • T-Lymphocytes / immunology*
  • Vaccines / immunology*

Substances

  • Cytokines
  • Vaccines