Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals

被引:107
作者
Cosma, A
Nagaraj, R
Bühler, S
Hinkula, J
Busch, DH
Sutter, G
Goebel, FD
Erfle, V
机构
[1] GSF, Natl Res Ctr Environm & Hlth, Inst Mol Virol, D-85764 Neuherberg, Germany
[2] Tech Univ Munich, Inst Virol, D-81675 Munich, Germany
[3] Karolinska Inst, Swedish Inst Infect Dis Control, Dept Virol, S-17182 Stockholm, Sweden
[4] Karolinska Inst, Microbiol & Tumorbiol Ctr, S-17182 Stockholm, Sweden
[5] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany
[6] Klinikum Ludwig Maximilians Univ, Med Poliklin, D-80336 Munich, Germany
关键词
nef; MVA; AIDS vaccines;
D O I
10.1016/S0264-410X(03)00538-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Vaccination is currently considered as an additional therapeutic approach to stimulate HIV-specific immune response in subjects that could not naturally control HIV. Ten chronically HIV infected individuals have been vaccinated with a modified vaccinia Ankara (MVA)-HIV- 1(LAI)-nef vector in order to assess safety and immunogenicity. No significant adverse effects were observed during the course of vaccination indicating for the first time that the highly attenuated vaccinia-vir-us vector MVA is safe in HIV-1 infected individuals. We observed a CD4 T-cell response to Nef in the majority of vaccinated chronically HIV infected individuals. In two subjects CD4 T-cell response was directed to previously unidentified Nef epitopes. The strong Nef-specific CD4 T-cell response elicited by MVA-nef vaccination provides a rationale for immunotherapeutic interventions in HIV infected individuals with suppressed CD4 T-cell responses. Moreover, the CD4 T-cell response elicited was comparable with that usually detected in long-term non-progressor (LTNP) suggesting an improvement in the immunological status of the vaccinated subjects. Furthermore, the new putative CD4 epitopes described here hold promise as important tools for epitope-based vaccination. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:21 / 29
页数:9
相关论文
共 39 条
[1]   Smallpox vaccination and patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome [J].
Bartlett, JG .
CLINICAL INFECTIOUS DISEASES, 2003, 36 (04) :468-471
[2]   ENHANCED ESTABLISHMENT OF A VIRUS CARRIER STATE IN ADULT CD4+ T-CELL-DEFICIENT MICE [J].
BATTEGAY, M ;
MOSKOPHIDIS, D ;
RAHEMTULLA, A ;
HENGARTNER, H ;
MAK, TW ;
ZINKERNAGEL, RM .
JOURNAL OF VIROLOGY, 1994, 68 (07) :4700-4704
[3]   Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses:: Relationship to viral load in untreated HIV infection [J].
Betts, MR ;
Ambrozak, DR ;
Douek, DC ;
Bonhoeffer, S ;
Brenchley, JM ;
Casazza, JP ;
Koup, RA ;
Picker, LJ .
JOURNAL OF VIROLOGY, 2001, 75 (24) :11983-11991
[4]   Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus [J].
Borrow, P ;
Lewicki, H ;
Wei, XP ;
Horwitz, MS ;
Peffer, N ;
Meyers, H ;
Nelson, JA ;
Gairin, JE ;
Hahn, BH ;
Oldstone, MBA ;
Shaw, GM .
NATURE MEDICINE, 1997, 3 (02) :205-211
[5]   VIRUS-SPECIFIC CD8+ CYTOTOXIC T-LYMPHOCYTE ACTIVITY ASSOCIATED WITH CONTROL OF VIREMIA IN PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION [J].
BORROW, P ;
LEWICKI, H ;
HAHN, BH ;
SHAW, GM ;
OLDSTONE, MBA .
JOURNAL OF VIROLOGY, 1994, 68 (09) :6103-6110
[6]  
Calarota SA, 1999, J IMMUNOL, V163, P2330
[7]   Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy [J].
Casazza, JP ;
Betts, MR ;
Picker, LJ ;
Koup, RA .
JOURNAL OF VIROLOGY, 2001, 75 (14) :6508-6516
[8]   HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes [J].
Collins, KL ;
Chen, BK ;
Kalams, SA ;
Walker, BD ;
Baltimore, D .
NATURE, 1998, 391 (6665) :397-401
[9]   HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression [J].
Davey, RT ;
Bhat, N ;
Yoder, C ;
Chun, TW ;
Metcalf, JA ;
Dewar, R ;
Natarajan, V ;
Lempicki, RA ;
Adelsberger, JW ;
Millers, KD ;
Kovacs, JA ;
Polis, MA ;
Walker, RE ;
Falloon, L ;
Masur, H ;
Gee, D ;
Baseler, M ;
Dimitrov, DS ;
Fauci, AS ;
Lane, HC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15109-15114
[10]  
Drexler I, 1999, CANCER RES, V59, P4955