Immunization with a Combination of Integral Chlamydial Antigens and a Defined Secreted Protein Induces Robust Immunity against Genital Chlamydial Challenge
Immunization with a Combination of Integral Chlamydial Antigens and a Defined Secreted Protein Induces Robust Immunity against Genital Chlamydial Challenge
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DOI：
10.1128/iai.00346-10
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发表时间：
2010-09-01
影响因子：
3.1
通讯作者：
Arulanandam, Bernard P.
中科院分区：
文献类型：
--
作者：
Li, Weidang;Murthy, Ashlesh K.;Arulanandam, Bernard P.
我们以前已经证明了重组衣原体蛋白酶样活性因子（rCPAF;分泌的衣原体蛋白）在诱导抗原特异性CD 4（+）T细胞/γ干扰素（IFN-γ）介导而非抗体介导的衣原体清除和减少上生殖道（UGT）病理后遗症方面的疗效。由于衣原体整合抗原可能诱导中和抗体保护，我们进一步评估了使用rCPAF和UV灭活衣原体初级体（UV-EB）组合对抗阴道衣原体攻击的保护性免疫诱导，并与使用单个组分或活EB的免疫进行比较。rCPAF-UV-EB免疫诱导了显著增强的抗UV-EB细胞和抗体应答，以及降低的抗CPAF细胞和抗体应答，与用各自的单独组分免疫相比。此外，接种UV-EB和rCPAF-UV-EB诱导血清抗体，中和衣原体感染性。rCPAF-UV-EB免疫导致阴道衣原体脱落的显著减少，并诱导比用单个组分接种小鼠更早的细菌清除。重要的是，在用rCPAF或rCPAF-UV-EB免疫的小鼠中，UGT后遗症显著减少，但在单独用UV-EB免疫的小鼠中没有，并且接近由活EB诱导的保护水平。这些结果共同表明，由完整衣原体抗原诱导的中和抗体和由分泌蛋白如CPAF诱导的细胞介导的应答的组合诱导针对生殖器衣原体感染的最佳保护性免疫。
We have previously demonstrated the efficacy of recombinant chlamydial protease-like activity factor (rCPAF; a secreted chlamydial protein) in inducing antigen-specific CD4(+) T cell/gamma interferon (IFN-gamma)-mediated but not antibody-mediated chlamydial clearance and reduction of upper genital tract (UGT) pathological sequelae. Since chlamydial integral antigens may induce neutralizing antibody protection, we further evaluated induction of protective immunity using a combination of rCPAF and UV-inactivated chlamydial elementary bodies (UV-EB) against vaginal chlamydial challenge in comparison to immunization with the individual components or live EB. The rCPAF-UV-EB immunization induced a significantly enhanced anti-UV-EB cellular and antibody response and a reduced anti-CPAF cellular and antibody response, compared to immunization with the respective individual components. Moreover, vaccination with UV-EB and rCPAF-UV-EB induced serum antibodies that neutralized chlamydial infectivity. The rCPAF-UV-EB immunization resulted in a significant reduction of vaginal chlamydial shedding and induced earlier bacterial clearance than vaccination of mice with the individual components. Importantly, the UGT sequelae were significantly reduced in mice immunized with rCPAF or rCPAF-UV-EB, but not in those immunized with UV-EB alone, and approached the levels of protection induced by live EB. These results collectively suggest that a combination of neutralizing antibodies induced by integral chlamydial antigens and cell-mediated responses induced by secreted proteins such as CPAF induces optimal protective immunity against genital chlamydial infections.