title: Pushing the frontiers of T-cell vaccines: accurate measurement of human T-cell responses.
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.
authors.affiliation: Vaxine Pty Ltd, Bedford Park, Adelaide 5042, Australia.
authors.forename: Fadi
authors.initials: F
authors.lastname: Saade
authors.forename: Stacey Ann
authors.initials: SA
authors.lastname: Gorski
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
mesh_terms: D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D007118:Immunoassay / Q000379:methods*; D007156:Immunologic Memory; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
chemical_list: D016207:Cytokines; D014612:Vaccines