Humoral and cellular immune responses to airway immunization of mice with human papillomavirus type 16 virus-like particles and mucosal adjuvants.
Humoral and cellular immune responses to airway immunization of mice with human papillomavirus type 16 virus-like particles and mucosal adjuvants.
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DOI：
10.1016/j.antiviral.2007.05.005
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发表时间：
2007-10
影响因子：
7.6
通讯作者：
Véronique Revaz;R. Zurbriggen;C. Moser;J. Schiller;Françoise Ponci;M. Bobst;D. Nardelli-Haefliger
中科院分区：
文献类型：
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作者：
Véronique Revaz;R. Zurbriggen;C. Moser;J. Schiller;Françoise Ponci;M. Bobst;D. Nardelli-Haefliger
宫颈癌是由人乳头瘤病毒（HPV），特别是HPV 16引起的宫颈感染引起的。肌内注射HPV 16病毒样颗粒（VLP）疫苗已被证明可诱导强烈的中和抗体应答，并保护女性免受生殖器HPV 16感染和相关病变。然而，避免胃肠外注射的替代给药途径可能有助于疫苗的实施，特别是在占世界宫颈癌病例大多数的发展中国家。此外，诱导粘膜免疫可以部分克服排卵期妇女宫颈HPV 16抗体的实质性变化。先前已证明，用HPV 16 VLP进行的气溶胶疫苗接种在小鼠和女性中具有免疫原性。在这里，我们研究是否暴露于其他呼吸道病毒抗原可能会干扰HPV 16 VLP特异性体液应答，以及两种已知的粘膜佐剂，CpG寡脱氧核苷酸和天然无毒的大肠杆菌不耐热肠毒素（HLT），是否可以增强HPV 16 VLP小鼠气道免疫（鼻或气溶胶样）的免疫原性。我们的数据显示，HLT可显著改善血清和粘膜分泌物中的抗VLP体液应答，以及CD 8 T细胞的VLP特异性增殖应答和IFN-γ产生，并且近期暴露于流感表面抗原可减少粘膜而非全身对VLP的抗体应答。
Cervical cancer results from cervical infection by human papillomaviruses (HPV), especially HPV16. Intramuscular administrations of HPV16 virus-like particle (VLP) vaccines have been shown to induce strong neutralizing antibody responses and protect women against genital HPV16 infection and associated lesions. However, an alternative route of administration that avoids parenteral injection might facilitate vaccine implementation, particularly in developing countries which account for the majority of the worldwide cases of cervical cancer. In addition, inducing mucosal immunity could partially overcome the substantial variation in HPV16 antibodies at the cervix seen in ovulating women. Aerosol vaccination with HPV16 VLPs was previously shown to be immunogenic in mice and in women. Here, we examine whether exposure to other respiratory viral antigens may interfere with the HPV16 VLP-specific humoral response and whether two known mucosal adjuvants, CpG oligodeoxynucleotides and a natural non-toxic Escherichia coli heat-labile enterotoxin (HLT), can enhance the immunogenicity of airway immunization (nasal or aerosol-like) of mice with HPV16 VLPs. Our data show that HLT can significantly improve anti-VLP humoral responses in serum and mucosal secretions, as well as VLP-specific proliferative responses and IFN-γ production by CD8 T cells, and that recent exposure to influenza surface antigens can diminish mucosal, but not systemic, antibody responses to the VLPs.