Nasal immunization of mice with peptide having a cross-neutralization epitope on minor capsid protein L2 of human papillomavirus type 16 elicit systemic and mucosal antibodies

Nasal immunization of mice with peptide having a cross-neutralization epitope on minor capsid protein L2 of human papillomavirus type 16 elicit systemic and mucosal antibodies
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DOI:
10.1016/s0264-410x(00)00367-4
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发表时间:
2001-01-08
期刊:
影响因子:
5.5
通讯作者:
Kanda, T
Kanda, T
中科院分区:
医学3区
文献类型:
--
作者:
Kawana, K;Kawana, Y;Kanda, T

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人乳头瘤病毒6型和16型(HPV 6和16)的共同交叉中和表位存在于HPV-16次要衣壳蛋白L2的氨基酸(aa)108-120的区域中。我们用具有13个氨基酸的HPV 16 L2序列的合成肽经鼻免疫Balb/c小鼠,并检查所引发的抗体。ELISA结果表明,免疫诱导主要IgG和IpA抗体交叉结合的L1/L2-衣壳的HPV 6,16和18在血清和阴道分泌物中,分别。含有IgG抗体的血清和含有伊加抗体的阴道洗液中和HPV 16假病毒体和HPV 11真实病毒体,如替代感染性测定所示。从它们对HPV 16和18的交叉结合活性来看,肽诱导的抗体可能可以交叉中和大多数生殖器HPV。阴道洗液中肽诱导的中和活性与用HPV 16 L1-衣壳经鼻免疫诱导的中和活性相当。与Balb/c、C57 BL/10不同。其具有不同的MHC II类,对肽免疫没有应答,但是肽中的氨基酸取代以满足对C57 BL/10抗原表位的要求使得修饰的肽具有免疫原性。这些结果为开发针对人生殖道广谱HPV的肽疫苗提供了基础。(C)2001爱思唯尔科技有限公司版权所有。
A common cross-neutralization epitope for human papillomavirus types 6 and 16 (HPV 6 and 16) is present in the region of amino acids (aa) 108-120 of HPV-16 minor capsid protein, L2. We nasally immunized Balb/c mice with a synthetic peptide with the 13 aa HPV 16 L2 sequence, and examined the antibodies elicited. ELISA showed that the immunization induced predominantly IgG and IpA antibodies cross-binding to L1/L2-capsids of HPVs 6, 16, and 18 in sera and in vaginal secretions, respectively. The serum containing the IgG antibody and the vaginal wash containing the IgA antibody neutralized HPV 16 pseudovirions and HPV 11 authentic virions, as shown by surrogate infectivity assays. From their cross-binding activity for HPV 16 and 18, the peptide-induced antibodies can probably cross-neutralize most of the genital HPVs. The peptide-induced neutralizing activity in vaginal wash was comparable to that induced by nasally immunization with HPV 16 L1-capsids. Unlike Balb/c, C57BL/10. which has different MHC class II, did not respond to the peptide immunization, but aa substitutions in the peptide to fulfill the requirement for the C57BL/10 agretope rendered the modified peptides immunogenic. The results provide a basis for development of a peptide vaccine against broad-spectrum of genital HPVs for humans. (C) 2001 Elsevier Science Ltd. All rights reserved.