Comparison of immune responses and protective efficacy of intranasal prime-boost immunization regimens using adenovirus-based and CpG/HH2 adjuvanted-subunit vaccines against genital Chlamydia muridarum infection

被引:25
作者
Brown, Tyler H. T. [1 ,2 ]
David, Jason [1 ,2 ]
Acosta-Ramirez, Elizabeth [1 ,2 ]
Moore, Jessica M. [1 ,2 ]
Lee, Song [2 ,3 ]
Zhong, Guangming [4 ]
Hancock, Robert E. W. [5 ]
Xing, Zhou [6 ,7 ]
Halperin, Scott A. [1 ,2 ,3 ]
Wang, Jun [1 ,2 ,3 ]
机构
[1] Dalhousie Univ, IWK Hlth Ctr, Canadian Ctr Vaccinol, Halifax, NS B3K 6R8, Canada
[2] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3K 6R8, Canada
[3] Dalhousie Univ, Dept Pediat, Halifax, NS B3K 6R8, Canada
[4] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA
[5] Univ British Columbia, Dept Microbiol & Immunol, Ctr Microbial Dis & Immun Res, Vancouver, BC V5Z 1M9, Canada
[6] McMaster Univ, Ctr Gene Therapeut, Dept Pathol & Mol Med, Hamilton, ON, Canada
[7] McMaster Univ, MG DeGroote Inst Infect Dis Res, Hamilton, ON, Canada
基金
加拿大健康研究院;
关键词
Adenovirus; CPAF; CpG; HH2; Adjuvant; Chlamydia; Th1; Th17; Heterologous prime-boost; Homologous prime-boost; Vaccination; DEFENSE REGULATOR PEPTIDE; CD4(+) T-CELLS; PULMONARY TUBERCULOSIS; MUCOSAL IMMUNIZATION; INTESTINAL INFLAMMATION; VECTORED TUBERCULOSIS; GAMMA-INTERFERON; TRACT INFECTION; SINGLE MUCOSAL; IFN-GAMMA;
D O I
10.1016/j.vaccine.2011.10.086
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
An efficacious Chlamydia vaccine is urgently needed to control Chlamydia infections. Heterologous prime-boost vaccination regimens are emerging as a promising strategy for preventing intracellular viral and bacterial infections. However, it remains to be determined if this regimen would be a feasible and effective approach for Chlamydia infection. In this study, we examined the immune response and the protective efficacy induced by various vaccination regimens using a recombinant adenovirus vector expressing the Chlamydia antigen CPAF (AdCPAF) and recombinant CPAF (rCPAF) subunit vaccines formulated with CpG oligodeoxynucleotides and/or a synthetic immunomodulatory peptide HH2 as adjuvants. A single dose of AdCPAF stimulated potent antibody production but weak cellular immune responses in mice. A booster rCPAF vaccine formulated with both CpG and HH2, but not CpG alone or HH2 alone, showed robust adjuvant effects on induction of Th1-biased cellular immune responses in mice primed with AdCPAF. In contrast, a homologous regimen using rCPAF/CpG/HH2 subunit vaccine for both priming and boosting induced a weak antibody response, but potent cellular immunity with a mixed Th1/Th17 profile. Despite the disparities observed in humoral and cellular immune responses, both the heterologous and homologous prime-boost regimens conferred significant immune protection against genital Chlamydia muridarum challenge in C3H/HeN and BALB/c mice. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:350 / 360
页数:11
相关论文
共 49 条
[1]   IL-17A directly inhibits TH1 cells and thereby suppresses development of intestinal inflammation [J].
Awasthi, Amit ;
Kuchroo, Vijay K. .
NATURE IMMUNOLOGY, 2009, 10 (06) :568-570
[2]   IL-17/Th17 Promotes Type 1 T Cell Immunity against Pulmonary Intracellular Bacterial Infection through Modulating Dendritic Cell Function [J].
Bai, Hong ;
Cheng, Jianjun ;
Gao, Xiaoling ;
Joyee, Antony George ;
Fan, Yijun ;
Wang, Shuhe ;
Jiao, Lei ;
Yao, Zhi ;
Yang, Xi .
JOURNAL OF IMMUNOLOGY, 2009, 183 (09) :5886-5895
[3]   Immunology of Chlamydia infection:: Implications for a Chlamydia trachomatis vaccine [J].
Brunham, RC ;
Rey-Ladino, J .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (02) :149-161
[4]   Synthetic innate defence regulator peptide enhances in vivo immunostimulatory effects of CpG-ODN in newborn piglets [J].
Cao, Ding ;
Li, Huazhou ;
Jiang, Zhenggu ;
Xu, Chenchao ;
Cheng, Qing ;
Yang, Zhaihan ;
Cao, Guangjun ;
Zhang, Linghua .
VACCINE, 2010, 28 (37) :6006-6013
[5]   Single intranasal mucosal Mycobactetium bovis BCG vaccination confers improved protection compared to subcutaneous vaccination against pulmonary tuberculosis [J].
Chen, LH ;
Wang, J ;
Zganiacz, A ;
Xing, Z .
INFECTION AND IMMUNITY, 2004, 72 (01) :238-246
[6]   TH 17 cells in development:: an updated view of their molecular identity and genetic programming [J].
Dong, Chen .
NATURE REVIEWS IMMUNOLOGY, 2008, 8 (05) :337-348
[7]   Production of a proteolytically active protein, chlamydial protease/proteasome-like activity factor, by five different Chlamydia species [J].
Dong, F ;
Zhong, YM ;
Arulanandam, B ;
Zhong, GM .
INFECTION AND IMMUNITY, 2005, 73 (03) :1868-1872
[8]   CD4+ T Cells and Antibody Are Required for Optimal Major Outer Membrane Protein Vaccine-Induced Immunity to Chlamydia muridarum Genital Infection [J].
Farris, Christina M. ;
Morrison, Sandra G. ;
Morrison, Richard P. .
INFECTION AND IMMUNITY, 2010, 78 (10) :4374-4383
[9]   Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization [J].
Gallichan, WS ;
Rosenthal, KL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (05) :1879-1890
[10]   SPECIFIC SECRETORY IMMUNE-RESPONSES IN THE FEMALE GENITAL-TRACT FOLLOWING INTRANASAL IMMUNIZATION WITH A RECOMBINANT ADENOVIRUS EXPRESSING GLYCOPROTEIN-B OF HERPES-SIMPLEX VIRUS [J].
GALLICHAN, WS ;
ROSENTHAL, KL .
VACCINE, 1995, 13 (16) :1589-1595