Berg Michael, Gambhira Ratish, Siracusa Mark, Hoiczyk Egbert, Roden Richard, Ketner Gary
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Vaccine. 2007 Apr 30;25(17):3501-10. doi: 10.1016/j.vaccine.2006.06.080. Epub 2006 Jul 18.
Immunization against human papillomavirus (HPV) infection promises to reduce the worldwide burden of cervical cancer. To evaluate the potential of live recombinant adenoviruses for induction of HPV infection-blocking immunity, we prepared viable adenovirus recombinants that express the HPV16 L1 gene from the adenovirus major late transcriptional unit. Adenovirus-produced HPV16 L1 assembles into virus-like particles (VLPs) in infected cells in culture. Purified HPV16 VLPs are recognized by HPV16 neutralizing antibodies and induce high neutralizing titers when injected intraperitoneally into mice. Canine oral papillomavirus VLPs derived from previously described recombinants also induce strong antibody responses in mice. These data support our suggestion that viable adenovirus recombinants will be able to induce protective immunity to papillomavirus infection during replication in human vaccinees.
人乳头瘤病毒(HPV)感染免疫接种有望减轻全球宫颈癌负担。为评估活重组腺病毒诱导HPV感染阻断免疫的潜力,我们制备了从腺病毒主要晚期转录单元表达HPV16 L1基因的活腺病毒重组体。腺病毒产生的HPV16 L1在培养的感染细胞中组装成病毒样颗粒(VLP)。纯化的HPV16 VLP可被HPV16中和抗体识别,并在腹腔注射到小鼠体内时诱导出高中和效价。源自先前描述的重组体的犬口腔乳头瘤病毒VLP在小鼠中也诱导出强烈的抗体反应。这些数据支持了我们的观点,即活腺病毒重组体将能够在人类疫苗接种者体内复制期间诱导针对乳头瘤病毒感染的保护性免疫。