Impact of cytotoxic-T-lymphocyte memory induction without virus-specific CD4+ T-Cell help on control of a simian immunodeficiency virus challenge in rhesus macaques.
Despite many efforts to develop AIDS vaccines eliciting virus-specific T-cell responses, whether induction of these memory T cells by vaccination before human immunodeficiency virus (HIV) exposure can actually contribute to effective T-cell responses postinfection remains unclear. In particular, induction of HIV-specific memory CD4(+) T cells may increase the target cell pool for HIV infection because the virus preferentially infects HIV-specific CD4(+) T cells. However, virus-specific CD4(+) helper T-cell responses are thought to be important for functional CD8(+) cytotoxic-T-lymphocyte (CTL) induction in HIV infection, and it has remained unknown whether HIV-specific memory CD8(+) T cells induced by vaccination without HIV-specific CD4(+) T-cell help can exert effective responses after virus exposure. Here we show the impact of CD8(+) T-cell memory induction without virus-specific CD4(+) T-cell help on the control of a simian immunodeficiency virus (SIV) challenge in rhesus macaques. We developed a prophylactic vaccine by using a Sendai virus (SeV) vector expressing a single SIV Gag(241-249) CTL epitope fused with enhanced green fluorescent protein (EGFP). Vaccination resulted in induction of SeV-EGFP-specific CD4(+) T-cell and Gag(241-249)-specific CD8(+) T-cell responses. After a SIV challenge, the vaccinees showed dominant Gag(241-249)-specific CD8(+) T-cell responses with higher effector memory frequencies in the acute phase and exhibited significantly reduced viral loads. These results demonstrate that virus-specific memory CD8(+) T cells induced by vaccination without virus-specific CD4(+) T-cell help could indeed facilitate SIV control after virus exposure, indicating the benefit of prophylactic vaccination eliciting virus-specific CTL memory with non-virus-specific CD4(+) T-cell responses for HIV control.
Tsukamoto
Tetsuo
T
International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Japan.
Takeda
Akiko
A
Yamamoto
Takuya
T
Yamamoto
Hiroyuki
H
Kawada
Miki
M
Matano
Tetsuro
T
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag / Q000276:immunology / Q000627:therapeutic use; D007156:Immunologic Memory; D008251:Macaca; D018449:SAIDS Vaccines / Q000276:immunology; D029082:Sendai virus; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D018449:SAIDS Vaccines