Avipox-based simian immunodeficiency virus (SIV) vaccines elicit a high frequency of SIV-specific CD4+ and CD8+ T-cell responses in vaccinia-experienced SIVmac251-infected macaques.
The ability of ALVAC- or fowlpox-based simian immunodeficiency virus (SIV) vaccines to boost SIV-specific CD4+ and CD8+ T-cell responses was tested in 10 vaccinia-experienced macaques infected with SIVmac251. The CD8+ T-cell response to the dominant Gag(181-189) CM9 was quantitated in seven Mamu-A*01-positive macaques by tetramer staining, by ex vivo cytotoxic T-lymphocyte (CTL) activity, and by intracellular cytokine staining (ICS) with the specific Gag(181-189) CM9 peptide. The overall CD8+ T-cell response to Gag was assessed using a peptide pool encompassing the entire Gag protein followed by measurement of TNF-alpha production in ICS assay. Similarly, virus-specific CD4+ T-cell responses were measured by ICS for TNF-alpha following stimulation with the Gag-overlapping peptide and by proliferative response following stimulation with purified p27 Gag. The two vaccine modalities effectively boosted both CD4+ and CD8+ SIV-specific T-cell response despite prior exposure to the vaccinia-derivative NYVAC vector, suggesting that sequential boosting with either avipox-based vector vaccine candidate is a realistic approach in immune therapy of human immunodeficiency virus type 1 (HIV-1)-infected individuals.
Nacsa
Janos
J
Basic Research Laboratory, National Cancer Institute, 41/D804 Bethesda, MD 20892-5055, USA. jn97w@nih.gov
Radaelli
Antonia
A
Edghill-Smith
Yvette
Y
Venzon
David
D
Tsai
Wen-Po
WP
Morghen
Carlo De Giuli
Cde G
Panicali
Dennis
D
Tartaglia
Jim
J
Franchini
Genoveffa
G
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D018150:Avipoxvirus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics; D015684:Gene Products, pol / Q000096:biosynthesis / Q000235:genetics; D005838:Genotype; D007111:Immunity, Cellular / Q000502:physiology*; D007115:Immunization Schedule; D018655:Lymphocyte Count; D008253:Macaca mulatta; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014615:Vaccinia / Q000276:immunology*
D000914:Antibodies, Viral; D016207:Cytokines; D015683:Gene Products, gag; D015684:Gene Products, pol; D012333:RNA, Messenger; D012367:RNA, Viral; D018449:SAIDS Vaccines