title: DNA/Ad5 vaccination with SIV epitopes induced epitope-specific CD4⁺ T cells, but few subdominant epitope-specific CD8⁺ T cells.
abstract: The goals of a T cell-based vaccine for HIV are to reduce viral peak and setpoint and prevent transmission. While it has been relatively straightforward to induce CD8(+) T cell responses against immunodominant T cell epitopes, it has been more difficult to broaden the vaccine-induced CD8(+) T cell response against subdominant T cell epitopes. Additionally, vaccine regimens to induce CD4(+) T cell responses have been studied only in limited settings. In this study, we sought to elicit CD8(+) T cells against subdominant epitopes and CD4(+) T cells using various novel and well-established vaccine strategies. We vaccinated three Mamu-A*01(+) animals with five Mamu-A*01-restricted subdominant SIV-specific CD8(+) T cell epitopes. All three vaccinated animals made high frequency responses against the Mamu-A*01-restricted Env TL9 epitope with one animal making a low frequency CD8(+) T cell response against the Pol LV10 epitope. We also induced SIV-specific CD4(+) T cells against several MHC class II DRBw*606-restricted epitopes. Electroporated DNA with pIL-12 followed by a rAd5 boost was the most immunogenic vaccine strategy. We induced responses against all three Mamu-DRB*w606-restricted CD4 epitopes in the vaccine after the DNA prime. Ad5 vaccination further boosted these responses. Although we successfully elicited several robust epitope-specific CD4(+) T cell responses, vaccination with subdominant MHC class I epitopes elicited few detectable CD8(+) T cell responses. Broadening the CD8(+) T cell response against subdominant MHC class I epitopes was, therefore, more difficult than we initially anticipated.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Drive, Madison, WI 53711, USA.
authors.forename: Lara
authors.initials: L
authors.lastname: Vojnov
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Bean
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Peterson
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Chiuchiolo
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.forename: Ferencz S
authors.initials: FS
authors.lastname: Denes
authors.forename: Matyas
authors.initials: M
authors.lastname: Sandor
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Fuller
authors.forename: James T
authors.initials: JT
authors.lastname: Fuller
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Parks
authors.forename: Adrian B
authors.initials: AB
authors.lastname: McDermott
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016056:Immunodominant Epitopes; D018664:Interleukin-12; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; C110764:Mamu-A 01 antigen; D019444:Vaccines, DNA; D014764:Viral Proteins; D018664:Interleukin-12