Mucosal delivery of the human immunodeficiency virus-1 Tat protein in mice elicits systemic neutralizing antibodies, cytotoxic T lymphocytes and mucosal IgA

被引:29
作者
Marinaro, M
Riccomi, A
Rappuoli, R
Pizza, M
Fiorelli, V
Tripiciano, A
Cafaro, A
Ensoli, B
De Magistris, MT
机构
[1] Ist Super Sanita, Lab Bacteriol & Med Mycol, I-00161 Rome, Italy
[2] Chiron Spa, I-53100 Siena, Italy
[3] Ist Super Sanita, Virol Lab, I-00161 Rome, Italy
关键词
mucosal vaccines; adjuvants; HIV-1 Tat protein;
D O I
10.1016/S0264-410X(03)00295-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Human immunodeficiency virus (HIV)-1 Tat protein induces protection in non-human primates upon systemic vaccination. In view of the design of mucosal vaccines against HIV-1 we studied the immune response to native Tat (aa 1-86) in mice following intranasal delivery of the protein with two mucosal adjuvants, Escherichia coli heat-labile enterotoxin (LT) and LT-R72, a non-toxic mutant of LT. Immunization with Tat and the two adjuvants induced in BALB/c but not in C57BL/6 mice high and persistent levels of serum IgG and secretory IgA in vaginal and intestinal fluids. Mice sera neutralized Tat and recognized two epitopes mapping in the regions 1-20 and 46-60. Furthermore, their splenocytes proliferated and secreted IFN-gamma and IL-6 in response to Tat. Finally, CTLs were also elicited and they recognized an epitope localized within aa 11-40 of Tat. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:3972 / 3981
页数:10
相关论文
共 56 条
[1]   The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals [J].
Addo, MM ;
Altfeld, M ;
Rosenberg, ES ;
Eldridge, RL ;
Philips, MN ;
Habeeb, K ;
Khatri, A ;
Brander, C ;
Robbins, GK ;
Mazzara, GP ;
Goulder, PJR ;
Walker, BD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (04) :1781-1786
[2]   Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia [J].
Allen, TM ;
O'Connor, DH ;
Jing, PC ;
Dzuris, JL ;
Mothé, BR ;
Vogel, TU ;
Dunphy, E ;
Liebl, ME ;
Emerson, C ;
Wilson, N ;
Kunstman, KJ ;
Wang, XC ;
Allison, DB ;
Hughes, AL ;
Desrosiers, RC ;
Altman, JD ;
Wolinsky, SM ;
Sette, A ;
Watkins, DI .
NATURE, 2000, 407 (6802) :386-390
[3]   Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection [J].
Baba, TW ;
Liska, V ;
Hofmann-Lehmann, R ;
Vlasak, J ;
Xu, WD ;
Ayehunie, S ;
Cavacini, LA ;
Posner, MR ;
Katinger, H ;
Stiegler, G ;
Bernacky, BJ ;
Rizvi, TA ;
Schmidt, R ;
Hill, LR ;
Keeling, ME ;
Lu, YC ;
Wright, JE ;
Chou, TC ;
Ruprecht, RM .
NATURE MEDICINE, 2000, 6 (02) :200-206
[4]  
Barillari G, 1999, BLOOD, V94, P663
[5]   Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type I highly exposed, persistently seronegative female sex workers in northern Thailand [J].
Beyrer, C ;
Artenstein, AW ;
Rugpao, S ;
Stephens, H ;
VanCott, TC ;
Robb, ML ;
Rinkaew, M ;
Birx, DL ;
Khamboonruang, C ;
Zimmerman, PA ;
Nelson, KE ;
Natpratan, C .
JOURNAL OF INFECTIOUS DISEASES, 1999, 179 (01) :59-67
[6]   CHARACTERIZATION OF MURINE MONOCLONAL-ANTIBODIES TO THE TAT PROTEIN FROM HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 [J].
BRAKE, DA ;
GOUDSMIT, J ;
KRONE, WJA ;
SCHAMMEL, P ;
APPLEBY, N ;
MELOEN, RH ;
DEBOUCK, C .
JOURNAL OF VIROLOGY, 1990, 64 (02) :962-965
[7]   In vivo migration and function of transferred HIV-1-specific cytotoxic T cells [J].
Brodie, SJ ;
Lewinsohn, DA ;
Patterson, BK ;
Jiyamapa, D ;
Krieger, J ;
Corey, L ;
Greenberg, PD ;
Riddell, SR .
NATURE MEDICINE, 1999, 5 (01) :34-41
[8]   Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine [J].
Cafaro, A ;
Caputo, A ;
Fracasso, C ;
Maggiorella, MT ;
Goletti, D ;
Baroncelli, S ;
Pace, M ;
Sernicola, L ;
Koanga-Mogtomo, ML ;
Betti, M ;
Borsetti, A ;
Belli, R ;
Åkerblom, L ;
Corrias, F ;
Buttò, S ;
Heeney, J ;
Verani, P ;
Titti, F ;
Ensoli, B .
NATURE MEDICINE, 1999, 5 (06) :643-650
[9]   Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P) [J].
Cafaro, A ;
Titti, F ;
Fracasso, C ;
Maggiorella, MT ;
Baroncelli, S ;
Caputo, A ;
Goletti, D ;
Borsetti, A ;
Pace, M ;
Fanales-Belasio, E ;
Ridolfi, B ;
Negri, DRM ;
Sernicola, L ;
Belli, R ;
Corrias, F ;
Macchia, I ;
Leone, P ;
Michelini, Z ;
ten Haaft, P ;
Buttò, S ;
Verani, P ;
Ensoli, B .
VACCINE, 2001, 19 (20-22) :2862-2877
[10]   SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccine [J].
Cafaro, A ;
Caputo, A ;
Maggiorella, MT ;
Baroncelli, S ;
Fracasso, C ;
Pace, M ;
Borsetti, A ;
Sernicola, L ;
Negri, DRM ;
Ten Haaft, P ;
Betti, M ;
Michelini, Z ;
Macchia, I ;
Fanales-Belasio, E ;
Belli, R ;
Corrias, F ;
Buttò, S ;
Verani, P ;
Titti, F ;
Ensoli, B .
JOURNAL OF MEDICAL PRIMATOLOGY, 2000, 29 (3-4) :193-208