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.
MeSH terms
-
Adenoviruses, Human / genetics
-
Adenoviruses, Human / immunology*
-
Administration, Intranasal
-
Administration, Oral
-
Animals
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / metabolism
-
CD8-Positive T-Lymphocytes / virology
-
Enzyme-Linked Immunosorbent Assay / methods
-
Epitopes, T-Lymphocyte / administration & dosage
-
Epitopes, T-Lymphocyte / immunology
-
Gene Products, env / administration & dosage
-
Gene Products, env / genetics
-
Gene Products, env / immunology
-
Gene Products, gag / administration & dosage
-
Gene Products, gag / genetics
-
Gene Products, gag / immunology
-
Genetic Vectors / administration & dosage
-
Genetic Vectors / immunology
-
Histocompatibility Antigens Class I / immunology*
-
Humans
-
Immunity, Cellular / genetics
-
Immunization, Secondary / methods
-
Immunodominant Epitopes / immunology*
-
Interferon-gamma / biosynthesis
-
Interferon-gamma / metabolism
-
Intubation, Intratracheal
-
Leukocytes, Mononuclear / chemistry
-
Leukocytes, Mononuclear / immunology
-
Lymph Nodes / chemistry
-
Lymph Nodes / cytology
-
Lymph Nodes / immunology
-
Lymphocyte Activation / genetics
-
Macaca mulatta
-
Protein Subunits / administration & dosage
-
Protein Subunits / genetics
-
Protein Subunits / immunology
-
Recombination, Genetic / immunology*
-
SAIDS Vaccines / administration & dosage
-
SAIDS Vaccines / genetics
-
SAIDS Vaccines / immunology*
-
Simian Acquired Immunodeficiency Syndrome / immunology
-
Simian Acquired Immunodeficiency Syndrome / prevention & control
-
Simian Acquired Immunodeficiency Syndrome / virology
-
Simian Immunodeficiency Virus / genetics
-
Simian Immunodeficiency Virus / immunology*
-
Staining and Labeling
-
Vaccines, Synthetic / administration & dosage
-
Vaccines, Synthetic / genetics
-
Vaccines, Synthetic / immunology*
-
Virus Replication / genetics
-
Virus Replication / immunology*
Substances
-
Epitopes, T-Lymphocyte
-
Gene Products, env
-
Gene Products, gag
-
Histocompatibility Antigens Class I
-
Immunodominant Epitopes
-
Mamu-A 01 antigen
-
Protein Subunits
-
SAIDS Vaccines
-
Vaccines, Synthetic
-
Interferon-gamma