Advantages of a synthetic peptide immunogen over a protein immunogen in the development of an anti-pilus vaccine for Pseudomonas aeruginosa.

Advantages of a synthetic peptide immunogen over a protein immunogen in the development of an anti-pilus vaccine for Pseudomonas aeruginosa.
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DOI:
10.1111/j.1747-0285.2009.00825.x
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发表时间:
2009-07
影响因子:
3
通讯作者:
Hodges RS
Hodges RS
中科院分区:
医学4区
文献类型:
--
作者:
Kao DJ;Hodges RS

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IV型菌毛是铜绿假单胞菌感染建立的重要黏附素。我们以前曾报道过一种针对菌毛主要结构亚基PilA的受体结合域的合成肽疫苗。受体结合域是位于pilin蛋白c末端的14个残基二硫环。本研究的目的是比较肽偶联物和蛋白质亚基免疫原的免疫原性,以确定哪种更适合用于抗毛疹疫苗。用天然PAK菌株pilin蛋白和合成的锁孔帽贝血青素受体结合域肽免疫BALB/c小鼠。一种具有混乱受体结合结构域的新型匹林蛋白被用来表征受体结合结构域特异性抗体。用合成肽偶联物免疫的动物对天然毛缕蛋白的效价高于用毛缕蛋白免疫的动物。此外,抗肽血清对完整的匹林受体结合域的亲和力显著高于抗匹林蛋白血清。这些结果对疫苗设计具有重要意义,并表明使用合成肽偶联物比亚基毛蛋白用于抗毛疹疫苗有显着优势。
The type IV pilus is an important adhesin in the establishment of infection by Pseudomonas aeruginosa. We have previously reported on a synthetic peptide vaccine targeting the receptor-binding domain of the main structural subunit of the pilus, PilA. The receptor-binding domain is a 14-residue disulfide loop at the C-terminal end of the pilin protein. The objective of this study was to compare the immunogenicity of a peptide-conjugate to a protein subunit immunogen to determine which was superior for use in an anti-pilus vaccine. BALB/c mice were immunized with the native PAK strain pilin protein and a synthetic peptide of the receptor-binding domain conjugated to keyhole limpet haemocyanin. A novel pilin protein with a scrambled receptor-binding domain was used to characterize receptor-binding domain-specific antibodies. The titres against the native pilin of the animals immunized with the synthetic peptide-conjugate were higher than the titres of animals immunized with the pilin protein. In addition, the affinities of anti-peptide sera for the intact pilin receptor-binding domain were significantly higher than affinities of anti-pilin protein sera. These results have significant implications for vaccine design and show that there are significant advantages in using a synthetic peptide-conjugate over a subunit pilin protein for an anti-pilus vaccine.
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期刊: SCIENCE
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期刊: BIOCHEMISTRY
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