Robust recall and long-term memory T-cell responses induced by prime-boost regimens with heterologous live viral vectors expressing human immunodeficiency virus type 1 Gag and Env proteins.
We investigated long-term memory and recall cellular immune responses to human immunodeficiency virus type 1 (HIV-1) Env and Gag proteins elicited by recombinant vesicular stomatitis viruses (VSVs) expressing Env and Gag. More than 7 months after a single vaccination with VSV-Env, approximately 6% of CD8(+) splenocytes stained with major histocompatibility complex class I tetramers containing the Env p18-I10 immunodominant peptide and showed a memory phenotype (CD44(Hi)). The level of tetramer-positive cells in memory was about 14% of the peak primary response. Recall responses elicited in these mice 5 days after boosting with a heterologous recombinant vaccinia virus expressing HIV-1 Env showed that 40 to 45% of CD8(+) splenocytes were tetramer positive and activated (CD62L(Lo)), and these cells produced gamma interferon after stimulation with Env peptide, indicating that they were functional. Five months after the boost, the long-term memory cell population (tetramer positive, CD44(Hi)) constituted 30% of the CD8(+) splenocytes. Recall responses to HIV-1 Gag were examined in mice primed with VSV recombinants expressing HIV-1 Gag protein and boosted with a vaccinia virus recombinant expressing Gag. Using this protocol, we found that approximately 40% of CD8(+) splenocytes were activated (CD62L(Lo)) and specific for a Gag immunodominant peptide (tetramer positive). The high-level Gag recall response elicited by the vaccinia virus-Gag was greater than that obtained by boosting with a VSV-Gag vector with a different VSV glycoprotein. The corresponding levels of CD44(Hi) memory cells were also higher long after boosting with vaccinia virus-Gag than after boosting with a glycoprotein exchange VSV-Gag. Our results show that VSV vectors elicit high-level memory CTL responses and that these can be amplified as much as six- to sevenfold using a heterologous boosting vector.
Haglund
Karl
K
Department of Pathology, Program in Microbiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Leiner
Ingrid
I
Kerksiek
Kristen
K
Buonocore
Linda
L
Pamer
Eric
E
Rose
John K
JK
D016915:AIDS Vaccines; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D015686:Gene Products, env; D015683:Gene Products, gag