Protection against Leishmania donovani infection by DNA vaccination:: increased DNA vaccination efficiency through inhibiting the cellular p53 response

被引：48

作者：

Ghosh, A ^{[1
]}

Labrecque, S ^{[1
]}

Matlashewski, G ^{[1
]}

机构：

[1] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada

来源：

VACCINE | 2001年 / 19卷 / 23-24期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

p53; DNA vaccine; HPV E6; Leishmania;

D O I：

10.1016/S0264-410X(01)00023-8

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

DNA-vaccination holds great promise for the future of vaccine development against infectious diseases. especially in developing countries, We therefore investigated the possibility of using DNA-vaccination against Leishmania donovani infection with the A2 virulence gene and whether inhibiting the cellular p53 response could increase the effectiveness of the A2 DNA vaccine. p53, also known as the guardian of the genome, is activated following DNA transfection and has pleotropic effects on cells. which could have adverse effects on the effectiveness of DNA-vaccination. Two major observations are reported within. First, vaccination with the A2 gene induced both humoral and cellular immune responses against A2 which provided significant protection against infection with L. donovani. Second, inhibition of p53 with human papillomavirus E6 resulted in higher expression of heterologous transfected genes in vitro and more efficient DNA-vaccination in vivo. These results have important implications for DNA vaccination against leishmaniasis and potentially against other infectious diseases. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：3169 / 3178

页数：10

共 45 条

[11]

GU ZM, 1994, ONCOGENE, V9, P629

[12] Leishmaniasis [J].

Herwaldt, BL .

LANCET, 1999, 354 (9185) :1191-1199

[13] Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G(1) arrest [J].

Huang, LC ;

Clarkin, KC ;

Wahl, GM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (10) :4827-4832

[14]

Iwasaki A, 1997, J IMMUNOL, V158, P4591

[15]

Kim JJ, 1997, J IMMUNOL, V158, P816

[16] CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma [J].

Klinman, DM ;

Yi, AK ;

Beaucage, SL ;

Conover, J ;

Krieg, AM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :2879-2883

[17] CANCER - P53, GUARDIAN OF THE GENOME [J].

LANE, DP .

NATURE, 1992, 358 (6381) :15-16

[18] The capacity to produce IFN-γ rather than the presence of interleukin-4 determines the resistance and the degree of susceptibility to Leishmania donovani infection in mice [J].

Lehmann, J ;

Enssle, KH ;

Lehmann, I ;

Emmendörfer, A ;

Lohmann-Matthes, ML .

JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2000, 20 (01) :63-77

[19] CD28/B7 system of T cell costimulation [J].

Lenschow, DJ ;

Walunas, TL ;

Bluestone, JA .

ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :233-258

[20] p53, the cellular gatekeeper for growth and division [J].

Levine, AJ .

CELL, 1997, 88 (03) :323-331

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