title: Different patterns of expansion, contraction and memory differentiation of HIV-1 Gag-specific CD8 T cells elicited by adenovirus type 5 and modified vaccinia Ankara vaccines.
abstract: The magnitude and functional quality of antiviral CD8 T cell responses are critical for the efficacy of T cell based vaccines. Here, we investigate the influence of two popular viral vectors, adenovirus type 5 (Ad5) and modified vaccinia Ankara (MVA), on expansion, contraction and memory differentiation of HIV-1 Gag insert-specific CD8 T cell responses following immunization and show different patterns for the two recombinant viral vectors. The Ad5 vector primed 6-fold higher levels of insert-specific CD8 effector T cells than the MVA vector. The Ad5-primed effector cells also underwent less contraction (<2-fold) than the MVA-primed cells (>5-fold). The Ad5-primed memory cells were predominantly CD62L negative (effector memory) whereas the MVA-primed memory cells were predominantly CD62L positive (central memory). Consistent with their memory phenotype, MVA-primed CD8 T cells underwent higher fold expansion than Ad5-primed CD8 T cells following a homologous or heterologous boost. Impressively, the Ad5 boost changed the quality of MVA-primed memory response such that they undergo less contraction with effector memory phenotype. However, the MVA boost did not influence the contraction and memory phenotype of Ad5-primed response. In conclusion, our results demonstrate that vaccine vector strongly influences the expansion, contraction and the functional quality of insert-specific CD8 T cell responses and have implications for vaccine development against infectious diseases.
authors.affiliation: Vaccine Research Center, Department of Microbiology and Immunology, Yerkes National Primate Research Center and Emory University School of Medicine, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
authors.forename: Vinod Kumar Bhaskara
authors.initials: VK
authors.lastname: Pillai
authors.forename: Sunil
authors.initials: S
authors.lastname: Kannanganat
authors.forename: Pablo
authors.initials: P
authors.lastname: Penaloza-Macmaster
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Chennareddi
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
authors.forename: Jerry
authors.initials: J
authors.lastname: Blackwell
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D004337:Drug Carriers; D005822:Genetic Vectors; D007156:Immunologic Memory; D019041:L-Selectin / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D054301:gag Gene Products, Human Immunodeficiency Virus; D019041:L-Selectin