Handisurya Alessandra, Gambhira Ratish, Schellenbacher Christina, Shafti-Keramat Saeed, Forslund Ola, Favre Michel, Kirnbauer Reinhard
Laboratory of Viral Oncology, Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna, Vienna, Austria.
J Gen Virol. 2009 Jan;90(Pt 1):136-43. doi: 10.1099/vir.0.006189-0.
Evidence of a possible association of cutaneous human papillomavirus (HPV) types, especially members of the genus Betapapillomavirus, and the development of non-melanoma skin cancer (NMSC) is accumulating. Vaccination with virus-like particles (VLPs) consisting of self-assembled L1, the major capsid protein, has been introduced to control anogenital HPV infection. This study examined the serological relationship between betapapillomavirus (beta-PV) types 5 and 8 and the new type HPV-92, which has recently been isolated from a basal cell carcinoma containing a high number of viral genomes. Following expression by recombinant baculoviruses, the L1 protein of HPV-92 self-assembled into VLPs that elicited high-titre antibodies after immunization, similar to VLPs from HPV-5 and -8. Haemagglutination inhibition (HAI) assays were used as a surrogate method for the detection of virion-neutralizing antibodies, which correlates with protection from infection. Antisera raised against HPV-5 and -8 VLPs displayed HAI activity not only against the homologous type, but also against heterologous HPV types 5, 8 and 92, whereas HAI activity of antisera against HPV-92 VLP was restricted to the homologous type. The results of neutralization assays using HPV-5 pseudovirions were consistent with those from HAI assays. Cross-neutralizing immune responses by VLP vaccination against heterologous HPV types may provide broader protection against the multiplicity of HPV types detected in NMSC. If a close link to HPV infection can be conclusively established, these results may provide a basis for further evaluation of VLPs of beta-PVs as candidates for a prophylactic skin-type HPV vaccine, aimed at reducing the incidence of NMSC.
皮肤人乳头瘤病毒(HPV)类型,尤其是β乳头瘤病毒属成员,与非黑素瘤皮肤癌(NMSC)发生之间可能存在关联的证据正在不断积累。由主要衣壳蛋白L1自组装而成的病毒样颗粒(VLP)疫苗已被用于控制肛门生殖器HPV感染。本研究检测了β乳头瘤病毒5型和8型与新型HPV-92之间的血清学关系,HPV-92最近从一个含有大量病毒基因组的基底细胞癌中分离得到。经重组杆状病毒表达后,HPV-92的L1蛋白自组装成VLP,免疫后可诱导产生高滴度抗体,类似于HPV-5和-8的VLP。血凝抑制(HAI)试验被用作检测病毒体中和抗体的替代方法,该抗体与预防感染相关。针对HPV-5和-8 VLP产生的抗血清不仅对同源型显示HAI活性,而且对异源HPV类型5、8和92也显示HAI活性,而针对HPV-92 VLP的抗血清的HAI活性仅限于同源型。使用HPV-5假病毒颗粒进行中和试验的结果与HAI试验结果一致。VLP疫苗接种针对异源HPV类型的交叉中和免疫反应可能为预防NMSC中检测到的多种HPV类型提供更广泛的保护。如果能最终确定与HPV感染的密切联系,这些结果可能为进一步评估β-PV的VLP作为预防性皮肤型HPV疫苗候选物提供依据,旨在降低NMSC的发病率。