title: T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge.
abstract: Determining the "correlates of protection" is one of the challenges in human immunodeficiency virus vaccine design. To date, T-cell-based AIDS vaccines have been evaluated with validated techniques that measure the number of CD8(+) T cells in the blood that secrete cytokines, mainly gamma interferon (IFN-gamma), in response to synthetic peptides. Despite providing accurate and reproducible measurements of immunogenicity, these methods do not directly assess antiviral function and thus may not identify protective CD8(+) T-cell responses. To better understand the correlates of vaccine efficacy, we analyzed the immune responses elicited by a successful T-cell-based vaccine against a heterologous simian immunodeficiency virus challenge. We searched for correlates of protection using a viral suppression assay (VSA) and an IFN-gamma enzyme-linked immunospot assay. While the VSA measured in vitro suppression, it did not predict the outcome of the vaccine trial. However, we found several aspects of the vaccine-induced T-cell response that were associated with improved outcome after challenge. Of note, broad vaccine-induced prechallenge T-cell responses directed against Gag and Vif correlated with lower viral loads and higher CD4(+) lymphocyte counts. These results may be relevant for the development of T-cell-based AIDS vaccines since they indicate that broad epitope-specific repertoires elicited by vaccination might serve as a correlate of vaccine efficacy. Furthermore, the present study demonstrates that certain viral proteins may be more effective than others as vaccine immunogens.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Dr., Madison, WI 53711, USA.
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Martins
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: Jason S
authors.initials: JS
authors.lastname: Reed
authors.forename: Chanook D
authors.initials: CD
authors.lastname: Ahn
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D015683:Gene Products, gag / Q000276:immunology; D016346:Gene Products, vif / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D016346:Gene Products, vif; D018449:SAIDS Vaccines; D007371:Interferon-gamma