Rose R C, White W I, Li M, Suzich J A, Lane C, Garcea R L
Departments of Medicine, Rochester, New York 14642; MedImmune, Inc., Gaithersburg, Maryland 20878, USA.
J Virol. 1998 Jul;72(7):6151-4. doi: 10.1128/JVI.72.7.6151-6154.1998.
The human papillomavirus type 11 (HPV-11) L1 major capsid protein can be trypsinized to generate recombinant capsomeres that retain HPV genotype-restricted capsid antigenicity (M. Li, T. P. Cripe, P. A. Estes, M. K. Lyon, R. C. Rose, and R. L. Garcea, J. Virol. 71:2988-2995, 1997). In the present study, HPV-11 virion-neutralizing monoclonal antibodies H11.F1 and H11.H3, previously characterized as recognizing two distinct HPV-11 capsid-neutralizing antigenic domains (S. W. Ludmerer, D. Benincasa, and G. E. Mark III, J. Virol. 70:4791-4794, 1996), were each found to be highly immunoreactive with trypsin-generated capsomeres in an enzyme-linked immunosorbent assay (ELISA). Capsomeres were used to generate high-titer polyclonal immune sera that demonstrated HPV genotype-restricted reactivity by ELISA. The capsomere antisera were then tested in an in vitro infectivity assay and found to neutralize HPV-11 virions. In this assay, HPV-11 capsomere polyclonal antisera exhibited neutralization titers (10(-5) to 10(-6)) comparable to those obtained with a virion-neutralizing antiserum raised previously against intact HPV-11 VLPs (R. C. Rose, R. C. Reichman, and W. Bonnez, J. Gen. Virol. 75:2075-2079, 1994). These results indicate that highly immunogenic, genotype-restricted HPV capsid-neutralizing antigenic domains are contained entirely within capsomeres. Thus, capsomeres may be viable vaccine candidates for the prevention of HPV disease.
人乳头瘤病毒11型(HPV - 11)的主要衣壳蛋白L1可经胰蛋白酶处理,生成保留HPV基因型限制衣壳抗原性的重组衣壳粒(M. 李、T. P. 克里普、P. A. 埃斯蒂斯、M. K. 里昂、R. C. 罗斯和R. L. 加尔塞亚,《病毒学杂志》71:2988 - 2995,1997年)。在本研究中,HPV - 11病毒体中和单克隆抗体H11.F1和H11.H3,先前被鉴定为识别两个不同的HPV - 11衣壳中和抗原结构域(S. W. 路德默勒、D. 贝宁卡萨和G. E. 马克三世,《病毒学杂志》70:4791 - 4794,1996年),在酶联免疫吸附测定(ELISA)中均被发现与胰蛋白酶生成的衣壳粒具有高度免疫反应性。衣壳粒被用于产生高效价多克隆免疫血清,该血清在ELISA中表现出HPV基因型限制的反应性。然后在体外感染性测定中对衣壳粒抗血清进行测试,发现其可中和HPV - 11病毒体。在该测定中,HPV - 11衣壳粒多克隆抗血清表现出的中和效价(10⁻⁵至10⁻⁶)与先前针对完整HPV - 11病毒样颗粒产生的病毒体中和抗血清所获得的效价相当(R. C. 罗斯、R. C. 赖克曼和W. 博内兹,《普通病毒学杂志》75:2075 - 2079,1994年)。这些结果表明,高度免疫原性、基因型限制的HPV衣壳中和抗原结构域完全包含在衣壳粒内。因此,衣壳粒可能是预防HPV疾病的可行疫苗候选物。