PEPTIDE POLYMERIZATION FACILITATES INCORPORATION INTO ISCOMS AND INCREASES ANTIGEN-SPECIFIC IGG2A PRODUCTION
PEPTIDE POLYMERIZATION FACILITATES INCORPORATION INTO ISCOMS AND INCREASES ANTIGEN-SPECIFIC IGG2A PRODUCTION
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DOI：
10.1016/0264-410x(95)00029-z
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发表时间：
1995-01-01
期刊：
影响因子：
5.5
通讯作者：
FRAZER, IH
中科院分区：
文献类型：
--
作者：
FERNANDO, GJP;STENZEL, DJ;FRAZER, IH
合成肽可以被量身定做，以包括从单个或多个抗原或生物体中获得的任何B或T表位。然而，多肽一般不是很有免疫原性，而且还没有被证明容易被结合到免疫原性疫苗中。ISCOMS是一种佐剂系统，不仅能够增强蛋白质的体液免疫原性，而且已经被证明能够在动物体内诱导细胞介导的免疫反应。合成肽ISCOM疫苗很少，因为很难将这些多肽结合到ISCOM中。我们在这项研究中已经证明，非免疫原性多肽可以通过聚合使其具有免疫原性，这些聚合物可以被掺入ISCOM中，以获得高度免疫原性的疫苗。人工合成的含有宫颈癌相关人乳头瘤病毒16型(HPV16E7)E7蛋白B和T辅助表位的20聚体多肽已被用作模型免疫原。我们比较了这些多肽作为聚合物或作为共聚物与脂类结合20肽(LAP 20)在ISCOM中掺入或不掺入时诱导的体液免疫。未聚合的多肽不能产生可测的抗体。当聚合肽与CFA或在无佐剂的磷酸盐缓冲液(PBS)中注射，或与ISCOMs结合时，ISCOms可产生识别免疫肽和HPV16E7蛋白的抗体，与CFA或PBS相比，ISCOms产生的抗体滴度更高。聚合肽诱导高的抗原特异性IgG2a：IgG1比值，并随着多次免疫的增加而增加。这些数据表明，聚合肽可以被整合到ISCOMS中，形成有效的免疫原，从而可能诱导Th1型应答
Synthetic peptides can be tailor-made to include any B or T epitopes desired from a single or multiple antigens or organisms. However, peptides in general are not very immunogenic and have not proven easy to incorporate into immunogenic vaccines. ISCOMs is an adjuvant system that has the capability not only to enhance the humoral immunogenicity of a protein but has also been shown to induce cell-mediated immune responses in animals. Synthetic peptide ISCOM vaccines are few because of the difficulty in incorporation of these peptides into ISCOMs. We have shown in this study, that non-immunogenic peptides could be made immunogenic by polymerisation, and these polymers could be incorporated into ISCOMs to give highly immunogenic vaccines. Synthetic 20mer peptides containing known B and T-helper epitopes from the E7 protein of the cervical cancer associated human papillomavirus type 16 (HPV16 E7) have been used here as model immunogens. We have compared the humoral immunity induced by these peptides as polymers or as copolymers with a lipid binding 20mer peptide (LAP 20), with or without incorporation into ISCOMs. Unpolymerised peptide elicited no measurable antibody. When polymerised peptide was administered with CFA, or in phosphate-buffered saline (PBS) without adjuvant, or incorporated into ISCOMs, antibodies recognising both the immunising peptide and HPV16 E7 protein weve produced For equal quantities of administered peptide (5 mu g), ISCOMs gave higher titres of antibody than CFA or PBS. Polymerised peptides induced high antigen-specific IgG2a:IgG1 ratios, which increased with multiple immunisations. These data indicate that polymerised peptides could be incorporated into ISCOMS to form efficient immunogens which may elicit a Th1 type repsonse