title: A replication competent adenovirus 5 host range mutant-simian immunodeficiency virus (SIV) recombinant priming/subunit protein boosting vaccine regimen induces broad, persistent SIV-specific cellular immunity to dominant and subdominant epitopes in Mamu-A*01 rhesus macaques.
abstract: CTL are important in controlling HIV and SIV infection. To quantify cellular immune responses induced by immunization, CD8(+) T cells specific for the subdominant Env p15m and p54m epitopes and/or the dominant Gag p11C epitope were evaluated by tetramer staining in nine macaques immunized with an adenovirus (Ad) 5 host range mutant (Ad5hr)-SIVenv/rev recombinant and in four of nine which also received an Ad5hr-SIVgag recombinant. Two Ad5hr-SIV recombinant priming immunizations were followed by two boosts with gp120 protein or an envelope polypeptide representing the CD4 binding domain. Two mock-immunized macaques served as controls. IFN-gamma-secreting cells were also assessed by ELISPOT assay using p11C, p15m, and p54m peptide stimuli and overlapping pooled Gag and Env peptides. As shown by tetramer staining, Ad-recombinant priming elicited a high frequency of persistent CD8(+) T cells able to recognize p11C, p15m, and p54m epitopes. The presence of memory cells 38 wk postinitial immunization was confirmed by expansion of tetramer-positive CD8(+) T cells following in vitro stimulation. The SIV-specific CD8(+) T cells elicited were functional and secreted IFN-gamma in response to SIV peptide stimuli. Although the level and frequency of response of peripheral blood CD8(+) T cells to the subdominant Env epitopes were not as great as those to the dominant p11C epitope, elevated responses were observed when lymph node CD8(+) T cells were evaluated. Our data confirm the potency and persistence of functional cellular immune responses elicited by replication competent Ad-recombinant priming. The cellular immunity elicited is broad and extends to subdominant epitopes.
authors.affiliation: Basic Research Laboratory, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Malkevitch
authors.forename: L Jean
authors.initials: LJ
authors.lastname: Patterson
authors.forename: Kristine
authors.initials: K
authors.lastname: Aldrich
authors.forename: Ersell
authors.initials: E
authors.lastname: Richardson
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Alvord
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D015686:Gene Products, env / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007117:Immunization, Secondary / Q000379:methods; D016056:Immunodominant Epitopes / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007442:Intubation, Intratracheal; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology; D008198:Lymph Nodes / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008253:Macaca mulatta; D021122:Protein Subunits / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic / Q000276:immunology*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013194:Staining and Labeling; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; C110764:Mamu-A 01 antigen; D021122:Protein Subunits; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma