Aerosol delivery of virus-like particles to the genital tract induces local and systemic antibody responses.

Aerosol delivery of virus-like particles to the genital tract induces local and systemic antibody responses.
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DOI:
10.1016/j.vaccine.2011.04.051
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发表时间:
2011-06-20
期刊:
影响因子:
5.5
通讯作者:
Chackerian, Bryce
Chackerian, Bryce
中科院分区:
医学3区
文献类型:
--
作者:
Hunter, Zoe;Tumban, Ebenezer;Dziduszko, Agnieszka;Chackerian, Bryce

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诱导生殖道粘膜免疫反应可能对提高性传播感染(STIs)疫苗的有效性很重要。在这项研究中,我们研究了用非复制病毒样颗粒(VLP)疫苗直接免疫小鼠生殖道是否能诱导局部粘膜和全身抗体反应。利用从两种噬菌体(Qβ和PP7)和一种通常感染生殖道的哺乳动物病毒(人乳头瘤病毒(HPV))中提取的VLPs,我们发现阴道内雾化给药VLPs可以在女性生殖道中诱导高滴度IgG和IgA抗体,并在血清中诱导IgG。利用小鼠HPV感染模型,我们发现阴道内接种HPV16型VLPs或PP7噬菌体VLPs,显示HPV次要衣壳蛋白L2衍生的肽,可以保护小鼠免受HPV16假病毒的生殖器感染。这些结果为使用基于vlp的免疫原诱导生殖器粘膜和全身抗体反应提供了一般方法。
The induction of mucosal immune responses in the genital tract may be important for increasing the effectiveness of vaccines for sexually transmitted infections (STIs). In this study, we asked whether direct immunization of the mouse genital tract with a non-replicating virus-like particle (VLP)-based vaccine could induce local mucosal as well as systemic antibody responses. Using VLPs derived from two bacteriophages, Qβ and PP7, and from a mammalian virus that normally infects the genital tract, human papillomavirus (HPV), we show that intravaginal aerosol administration of VLPs can induce high titer IgG and IgA antibodies in the female genital tract as well as IgG in the sera. Using a mouse model for HPV infection, we show that intravaginal immunization with either HPV type 16 VLPs or with PP7 bacteriophage VLPs displaying a peptide derived from the HPV minor capsid protein L2 could protect mice from genital infection with an HPV16 pseudovirus. These results provide a general method for inducing genital mucosal and systemic antibody responses using VLP-based immunogens.
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