Vaginal protection and immunity after oral immunization of mice with a novel vaccine strain of Listeria monocytogenes expressing human immunodeficiency virus type 1 gag

被引:20
作者
Zhao, Xinyan [1 ]
Zhang, Manxin [1 ]
Li, Zhongxia [1 ]
Frankel, Fred R. [1 ]
机构
[1] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA
关键词
D O I
10.1128/JVI.00894-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Natural transmission of human immunodeficiency virus (HIV) occurs at mucosal surfaces. During acute infection, intestinal and other mucosae are preferential sites of virus replication and rapidly become depleted of CD4(+) T cells. Therefore, mucosal immunity may be critical to control both initial infection and the massive early spread of virus. An attenuated D-alanine-requiring strain of the oral intracellular microorganism Listeria monocytogenes expressing HIV type 1 gag was shown to induce protective cell-mediated immunity in mice against viruses that express HIV gag when immunization occurs in the presence of a transient supply of D-alanine. In this study, we examined the efficacy of new attenuated strains that are able to synthesize D-alanine from a heterologous dal gene tightly regulated by an actA-promoted resolvase recombination system. In the absence Of D-alanine, Gag-specific cytotoxic T lymphocytes (CTLs) were induced systemically after intravenous immunization, and one strain, Lmdd-gag/pARS, induced strong dose-dependent Gag-specific CTLs after oral immunization. A significant level of Gag-specific CD8(+) T cells was induced in the mucosal-associated lymphoid tissues (MALTs). Upon intravaginal challenge of these orally immunized mice with recombinant vaccinia virus (rVV) expressing HIV gag, gamma interferon- and tumor necrosis factor alpha-secreting Gag-specific CD8(+) T cells were dramatically increased in the spleen and MALTs. Oral immunization with Lmdd-gag/pARS led to complete protection against vaginal challenge by a homologous clade B gag-expressing rVV. In addition, strong cross-clade protection was seen against clades A and C and partial protection against clade G gag-expressing rVV. These results suggest that Lmdd-gag/pARS may be considered as a novel vaccine candidate for use against HIV/AIDS.
引用
收藏
页码:8880 / 8890
页数:11
相关论文
共 55 条
[11]   Mucosal immunization with inactivated human immunodeficiency virus plus CpG oligodeoxynucleotides induces genital immune responses and protection against intravaginal challenge [J].
Dumais, N ;
Patrick, A ;
Moss, RB ;
Davis, HL ;
Rosenthal, KL .
JOURNAL OF INFECTIOUS DISEASES, 2002, 186 (08) :1098-1105
[12]   LISTERIA-MONOCYTOGENES, A FOOD-BORNE PATHOGEN [J].
FARBER, JM ;
PETERKIN, PI .
MICROBIOLOGICAL REVIEWS, 1991, 55 (03) :476-511
[13]   Complete protection of neonatal rhesus macaques against oral exposure to pathogenic simian-human immunodeficiency virus by human anti-HIV monoclonal antibodies [J].
Ferrantelli, F ;
Rasmussen, RA ;
Buckley, KA ;
Li, PL ;
Wang, T ;
Montefiori, DC ;
Katinger, H ;
Stiegler, G ;
Anderson, DC ;
McClure, HM ;
Ruprecht, RM .
JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (12) :2167-2173
[14]   Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers [J].
Ferrari, G ;
Humphrey, W ;
McElrath, MJ ;
Excler, JL ;
Duliege, AM ;
Clements, ML ;
Corey, LC ;
Bolognesi, DP ;
Weinhold, KJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (04) :1396-1401
[15]  
FRANKEL FR, 1995, J IMMUNOL, V155, P4775
[16]   Induction of human immunodeficiency virus (HIV)-specific CD8 T-cell responses by Listeria monocytogenes and a hyperattenuated Listeria strain engineered to express HIV antigens [J].
Friedman, RS ;
Frankel, FR ;
Xu, Z ;
Lieberman, J .
JOURNAL OF VIROLOGY, 2000, 74 (21) :9987-9993
[17]   ATTENUATED LISTERIA-MONOCYTOGENES AS A LIVE VECTOR FOR INDUCTION OF CD8(+) T-CELLS IN-VIVO - A STUDY WITH THE NUCLEOPROTEIN OF THE LYMPHOCYTIC CHORIOMENINGITIS VIRUS [J].
GOOSSENS, PL ;
MILON, G ;
COSSART, P ;
SARON, MF .
INTERNATIONAL IMMUNOLOGY, 1995, 7 (05) :797-805
[18]   The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system [J].
Gottesman, S ;
Roche, E ;
Zhou, YN ;
Sauer, RT .
GENES & DEVELOPMENT, 1998, 12 (09) :1338-1347
[19]   Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy [J].
Guadalupe, M ;
Reay, E ;
Sankaran, S ;
Prindiville, T ;
Flamm, J ;
McNeil, A ;
Dandekar, S .
JOURNAL OF VIROLOGY, 2003, 77 (21) :11708-11717
[20]   Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16 [J].
Gunn, GR ;
Zubair, A ;
Peters, C ;
Pan, ZK ;
Wu, TC ;
Paterson, Y .
JOURNAL OF IMMUNOLOGY, 2001, 167 (11) :6471-6479