Prophylactic immunization with human papillomavirus vaccines induces oral immunity in mice.
Prophylactic immunization with human papillomavirus vaccines induces oral immunity in mice.
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DOI：
10.1002/lary.26772
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Best SR
中科院分区：
文献类型：
--
作者：
Ahn J;Peng S;Hung CF;Roden RBS;Best SR
虽然已经证明预防性疫苗接种可以诱导生殖器免疫，但关于 HPV 疫苗诱导的口腔免疫的信息不足，由于 HPV 相关的口咽恶性肿瘤和复发性呼吸道乳头状瘤病，这一点特别令人感兴趣。因此，我们评估了各种HPV疫苗对小鼠口腔HPV假病毒感染的功效。临床前科学研究 C57BL/6 小鼠每隔 2 周接种 3 次加德西 (Gardasil)（50 μl 肌肉注射）或带有明矾佐剂的候选泛 HPV L2 疫苗（25 μg 皮下注射）。通过被动转移 Gardasil 人抗血清或未免疫血清（100 μL 腹腔注射）对另外的小鼠进行免疫。然后用口腔粘膜中的 HPV16 E6E7 荧光素酶假病毒攻击所有接种疫苗的小鼠和未接种疫苗的对照小鼠。使用 IVIS 光谱成像系统通过荧光素酶活性监测 HPV 假病毒感染的可视化。在 Gardasil、L2 疫苗和 Gardasil 抗血清免疫小鼠中未检测到表达口服荧光素酶的 HPV16 假病毒感染，而在所有对照小鼠中均观察到强荧光素酶表达。对接种加德西 (Gardasil) 疫苗的小鼠血清进行的体外中和测定证实了疫苗功效归因于中和抗体。所有预防性 HPV 免疫方法均能完全预防小鼠口腔 HPV16 假病毒感染。这些发现提供了初步证据，表明人类疫苗可以预防口腔 HPV 感染，这对 HPV 相关口咽恶性肿瘤具有重大的公共卫生影响。
While it has been shown that prophylactic vaccination can induce genital immunity, there is inadequate information on HPV vaccine-induced oral immunity, which is of particular interest due to HPV-associated oropharyngeal malignancies and Recurrent Respiratory Papillomatosis. Therefore, we assessed the efficacy of various HPV vaccines against oral HPV pseudovirus infection in mice. Pre-clinical scientific investigation C57BL/6 mice were vaccinated three times at 2-week intervals with either Gardasil (50 μl i.m.) or a candidate pan-HPV L2 vaccine with alum adjuvant (25 μg s.c.). Additional mice were immunized with passive transfer of either Gardasil human antisera or non-immunized sera (100 μL i.p.). All vaccinated and naïve control mice were then challenged with HPV16 E6E7 Luciferase pseudovirus in the oral mucosa. Visualization of HPV pseudovirus infection was monitored through luciferase activity using the IVIS Spectrum Imaging System. Oral Luciferase-expressing HPV16 pseudovirus infection was not detected in Gardasil, L2 vaccine and Gardasil antisera-immunized mice whereas robust Luciferase expression was observed in all control mice. An in vitro neutralization assay from sera of Gardasil-vaccinated mice confirmed vaccine efficacy was due to neutralizing antibodies. Oral HPV16 pseudovirus infection in mice was completely prevented with all methods of prophylactic HPV immunization. These findings provide preliminary evidence that human vaccines induce protection against oral HPV infection, which has significant public health implications for HPV-associated oropharyngeal malignancies.
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