Albumin-binding adenoviruses circumvent pre-existing neutralizing antibodies upon systemic delivery

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• 作者：Luis Alfonso Rojas^a ; Gabriela N. Condezo^b ; Rafael Moreno^a ; Carlos Alberto Fajardo^a ; Marcel Arias-Badia^a ; Carmen San Martí ; n^b ; Ramon Alemany^a ; ^{ralemany@iconcologia.net" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Adenovirus ; Albumin ; Albumin-binding domain ; Neutralizing antibodies
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 September 2016
• 年：2016
• 卷：237
• 期：Complete
• 页码：78-88
• 全文大小：1208 K

文摘

Recombinant adenoviruses are used as vaccines, gene therapy vectors, and oncolytic viruses. However, the efficacy of such therapies is limited by pre-existing neutralizing antibodies (NAbs), especially when the virus is administered systemically for a wider biodistribution or to reach multiple metastases. To protect adenovirus against NAbs we inserted an albumin-binding domain (ABD) in the main adenovirus capsid protein, the hexon. This domain binds serum albumin to shield the virus upon systemic administration. The ABD-modified adenoviruses bind human and mouse albumin and maintain the infectivity and replication capacity in presence of NAbs. In pre-immunized mice non-modified viruses are completely neutralized, whereas ABD-modified viruses preserve the ability to transduce target organs, induce oncolysis, or generate immune responses to expressed proteins. Our results indicate that albumin coating of the virus capsid represents an effective approach to evade pre-existing NAbs. This strategy has translational relevance in the use of adenovirus for gene therapy, cancer virotherapy, and vaccination.