Mucosal immunization with inactivated human immunodeficiency virus plus CpG oligodeoxynucleotides induces genital immune responses and protection against intravaginal challenge

被引:46
作者
Dumais, N
Patrick, A
Moss, RB
Davis, HL
Rosenthal, KL
机构
[1] McMaster Univ, Hlth Sci Ctr, Ctr Gene Therapeut, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada
[2] Coley Pharmaceut Grp, Ottawa, ON, Canada
[3] Immune Response Corp, Carlsbad, CA USA
关键词
D O I
10.1086/344232
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Vaccines capable of protecting against sexually transmitted infections, such as human immunodeficiency virus (HIV), will depend on the induction of potent long-lasting mucosal immune responses in the genital tract. We evaluated vaginal and systemic immune responses and protection from vaginal challenge elicited after intranasal immunization of mice with inactivated glycoprotien 120-depleted HIV-1 immunogen alone or in combination with immunostimulatory CpG oligodeoxynucleotides (ODNs). Mice immunized with HIV-1 immunogen plus CpG ODN had significantly enhanced levels of anti-protein 24 immunoglobulin (Ig) G and IgA antibodies in serum and vaginal washes and increased production of beta-chemokines and interferon-gamma, compared with mice immunized with HIV-1 immunogen alone or with control ODN. Furthermore, mice intranasally immunized with HIV-1 immunogen plus CpG were protected against intravaginal challenge with a recombinant vaccinia virus expressing HIV-1 gag. These results indicate that mucosal immunization with whole-killed HIV-1 plus CpG ODN may be an effective means of inducing local immunity and protection against genital infection.
引用
收藏
页码:1098 / 1105
页数:8
相关论文
共 56 条
[1]   Evaluation of the putative role of C-C chemokines as protective factors of HIV-1 infection in seronegative hemophiliacs exposed to contaminated hemoderivatives [J].
Barretina, J ;
Blanco, J ;
Gutiérrez, A ;
Puig, L ;
Altisent, C ;
Espanol, T ;
Caragol, I ;
Clotet, B ;
Esté, JA .
TRANSFUSION, 2000, 40 (04) :461-467
[2]   The importance of local mucosal HIV-specific CD8+ cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12 [J].
Belyakov, IM ;
Ahlers, JD ;
Brandwein, BY ;
Earl, P ;
Kelsall, BL ;
Moss, B ;
Strober, W ;
Berzofsky, JA .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (12) :2072-2081
[3]   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
[4]   Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques [J].
Belyakov, IM ;
Hel, Z ;
Kelsall, B ;
Kuznetsov, VA ;
Ahlers, JD ;
Nacsa, J ;
Watkins, DI ;
Allen, TM ;
Sette, A ;
Altman, J ;
Woodward, R ;
Markham, PD ;
Clements, JD ;
Franchini, G ;
Strober, W ;
Berzofsky, JA .
NATURE MEDICINE, 2001, 7 (12) :1320-1326
[5]   Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina [J].
Bergquist, C ;
Johansson, EL ;
Lagergard, T ;
Holmgren, J ;
Rudin, A .
INFECTION AND IMMUNITY, 1997, 65 (07) :2676-2684
[6]   HIV type 1 isolate Z321, the strain used to make a therapeutic HIV type 1 immunogen, is intersubtype recombinant [J].
Choi, DJ ;
Dube, S ;
Spicer, TP ;
Slade, HB ;
Jensen, FC ;
Poiesz, BJ .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 1997, 13 (04) :357-361
[7]   CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity [J].
Chu, RS ;
Targoni, OS ;
Krieg, AM ;
Lehmann, PV ;
Harding, CV .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (10) :1623-1631
[8]   IDENTIFICATION OF RANTES, MIP-1-ALPHA, AND MIP-1-BETA AS THE MAJOR HIV-SUPPRESSIVE FACTORS PRODUCED BY CD8(+) T-CELLS [J].
COCCHI, F ;
DEVICO, AL ;
GARZINODEMO, A ;
ARYA, SK ;
GALLO, RC ;
LUSSO, P .
SCIENCE, 1995, 270 (5243) :1811-1815
[9]  
Cowdery J, 1996, J IMMUNOL, V156, P4570
[10]   CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans [J].
Davis, HL ;
Suparto, I ;
Weeratna, R ;
Jumintarto ;
Iskandriati, D ;
Chamzah, S ;
Ma'ruf, A ;
Nente, C ;
Pawitri, D ;
Krieg, AM ;
Heriyanto ;
Smits, W ;
Sajuthi, D .
VACCINE, 2000, 18 (18) :1920-1924