Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env

被引:105
作者
Xin, KQ
Hoshino, Y
Toda, Y
Igimi, S
Kojima, Y
Jounai, N
Ohba, K
Kushiro, A
Kiwaki, M
Hamajima, K
Klinman, D
Okuda, K
机构
[1] Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[2] Food & Drug Adm Natl Hlth Inst, Rockville, MD USA
[3] Yakult Cent Inst Microbiol Res, Tokyo, Japan
[4] US FDA, Bethesda, MD 20014 USA
[5] Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA
关键词
D O I
10.1182/blood-2003-01-0110
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env-expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis-based HIV vaccines. (C) 2003 by The American Society of Hematology.
引用
收藏
页码:223 / 228
页数:6
相关论文
共 37 条
[1]   HUMORAL AND CELL-MEDIATED IMMUNE-RESPONSES TO LIVE RECOMBINANT BCG-HIV VACCINES [J].
ALDOVINI, A ;
YOUNG, RA .
NATURE, 1991, 351 (6326) :479-482
[2]   Phenotypic analysis of antigen-specific T lymphocytes [J].
Altman, JD ;
Moss, PAH ;
Goulder, PJR ;
Barouch, DH ;
McHeyzerWilliams, MG ;
Bell, JI ;
McMichael, AJ ;
Davis, MM .
SCIENCE, 1996, 274 (5284) :94-96
[3]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[4]   Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination [J].
Barouch, DH ;
Santra, S ;
Schmitz, JE ;
Kuroda, MJ ;
Fu, TM ;
Wagner, W ;
Bilska, M ;
Craiu, A ;
Zheng, XX ;
Krivulka, GR ;
Beaudry, K ;
Lifton, MA ;
Nickerson, CE ;
Trigona, WL ;
Punt, K ;
Freed, DC ;
Guan, LM ;
Dubey, S ;
Casimiro, D ;
Simon, A ;
Davies, ME ;
Chastain, M ;
Strom, TB ;
Gelman, RS ;
Montefiori, DC ;
Lewis, MG ;
Emini, EA ;
Shiver, JW ;
Letvin, NL .
SCIENCE, 2000, 290 (5491) :486-492
[5]   The effects of DNA containing CpG motif on dendritic cells [J].
Behboudi, S ;
Chao, D ;
Klenerman, P ;
Austyn, J .
IMMUNOLOGY, 2000, 99 (03) :361-366
[6]   Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge [J].
Belyakov, IM ;
Derby, MA ;
Ahlers, JD ;
Kelsall, BL ;
Earl, P ;
Moss, B ;
Strober, W ;
Berzofsky, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (04) :1709-1714
[7]   NEUTRALIZATION OF HIV-1 BY SECRETORY IGA INDUCED BY ORAL IMMUNIZATION WITH A NEW MACROMOLECULAR MULTICOMPONENT PEPTIDE VACCINE CANDIDATE [J].
BUKAWA, H ;
SEKIGAWA, KI ;
HAMAJIMA, K ;
FUKUSHIMA, J ;
YAMADA, Y ;
KIYONO, H ;
OKUDA, K .
NATURE MEDICINE, 1995, 1 (07) :681-685
[8]   Venezuelan equine encephalitis virus vectors expressing HIV-1 proteins: vector design strategies for improved vaccine efficacy [J].
Caley, IJ ;
Betts, MR ;
Davis, NL ;
Swanstrom, R ;
Frelinger, JA ;
Johnston, RE .
VACCINE, 1999, 17 (23-24) :3124-3135
[9]   Oral somatic transgene vaccination using attenuated S-typhimurium [J].
Darji, A ;
Guzman, CA ;
Gerstel, B ;
Wachholz, P ;
Timmis, KN ;
Wehland, J ;
Chakraborty, T ;
Weiss, S .
CELL, 1997, 91 (06) :765-775
[10]   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