Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys.
Since virus-specific CTL play a central role in containing HIV replication, a candidate AIDS vaccine should generate virus-specific CTL responses. In this study, the ability of a recombinant canarypox virus expressing SIV Gag-Pol-Env (ALVAC/SIV gag-pol-env) was assessed for its ability to elicit both dominant and subdominant epitope-specific CTL responses in rhesus monkeys. Following a series of five immunizations, memory CTL responses specific for a dominant Gag epitope could be demonstrated in the peripheral blood of vaccinated monkeys. Memory CTL responses to a subdominant Pol epitope were undetectable in these animals. Following challenge with SIVmac251, the experimentally vaccinated animals developed high frequency CTL responses specific for the dominant Gag epitope that emerged in temporal association with the early containment of viral replication. Interestingly, the experimentally vaccinated, but not the control vaccinated animals, developed CTL responses to the subdominant Pol epitope that were detectable only after containment of early viremia. Thus, recombinant canarypox vaccination elicited low frequency, but durable memory CTL populations. The temporal association of the emergence of the dominant epitope-specific response with early viral containment following challenge suggests that this immune response played a role in the accelerated clearing of early viremia in these animals. The later emerging CTL response specific for the subdominant epitope may contribute to the control of viral replication in the setting of chronic infection.
Santra
Sampa
S
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Schmitz
Jörn E
JE
Kuroda
Marcelo J
MJ
Lifton
Michelle A
MA
Nickerson
Christine E
CE
Lord
Carol I
CI
Pal
Ranajit
R
Franchini
Genoveffa
G
Letvin
Norman L
NL
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D028121:Canarypox virus / Q000235:genetics*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004279:DNA, Viral / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015684:Gene Products, pol / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D016056:Immunodominant Epitopes / Q000276:immunology*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology; D019562:Viral Load
D000956:Antigens, Viral; D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D016056:Immunodominant Epitopes; D018449:SAIDS Vaccines; D019444:Vaccines, DNA