An optimally constrained V3 peptide is a better immunogen than its linear homolog or HIV-1 gp120
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- 作者：Adi Moseri ; Subramanyam Tantry ; Yael Sagi ; Boris Arshava ; Fred Naider ; Jacob Anglister
- 关键词：HIV-1 ; Vaccine ; Neutralizing antibodies ; V3 loop ; Constrained peptides ; Gp120
- 刊名：Virology
- 出版年：2010
- 出版时间：5 June 2010
- 年：2010
- 卷：401
- 期：2
- 页码：293-304
- 全文大小：1121 K
文摘
Synthetic peptides offer an attractive option for development of a V3-directed vaccine. However, immunization with flexible linear peptides may result in an immune response to multiple conformations, many of which differ from the native conformation of the corresponding region in the protein. Here we show that optimization of the location of a disulfide bond in peptides constrained to mimic the β-hairpin conformation of the V3, yields an immunogen that elicits a 30-fold stronger HIV-1 neutralizing response in rabbits compared with the homologous linear V3 peptide. The HIV-1 neutralizing response elicited by the optimally constrained peptide is also significantly stronger than that elicited by a gp120 construct in which the V3 is exposed. Neutralization of an HIV-1 strain that shares only 72 % identity with the immunizing peptide was demonstrated. The most effective immunogen was also able to neutralize primary isolates that are more resistant to neutralization such as SS1196 and 6535.