Rapid Cloning of Novel Rhesus Adenoviral Vaccine Vectors

被引：30

作者：

Abbink, Peter ^{[1
]}

Kirilova, Marinela ^{[1
]}

Boyd, Michael ^{[1
]}

Mercado, Noe ^{[1
]}

Li, Zhenfeng ^{[1
]}

Nityanandam, Ramya ^{[1
]}

Nanayakkara, Ovini ^{[1
]}

Peterson, Rebecca ^{[1
]}

Larocca, Rafael A. ^{[1
]}

Aid, Malika ^{[1
]}

Tartaglia, Lawrence ^{[1
]}

Mutetwa, Tinaye ^{[1
]}

Blass, Eryn ^{[1
]}

Jetton, David ^{[1
]}

Maxfield, Lori F. ^{[1
]}

Borducchi, Erica N. ^{[1
]}

Badamchi-Zadeh, Alexander ^{[1
]}

Handley, Scott ^{[3
]}

Zhao, Guoyan ^{[3
]}

Virgin, Herbert W. ^{[3
]}

Havenga, Menzo J. ^{[4
]}

Barouch, Dan H. ^{[1
,2
]}

机构：

[1] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02115 USA

[2] Ragon Inst MGH MIT & Harvard, Boston, MA 02115 USA

[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

[4] AVVI Biotech, Boston, MA USA

来源：

JOURNAL OF VIROLOGY | 2018年 / 92卷 / 06期

关键词：

adenoviruses; live vector vaccines; rhesus monkey; vaccines; CHIMPANZEE ADENOVIRUS; PROTECTIVE EFFICACY; MONKEY ADENOVIRUS; IMMUNOGENICITY; CONSTRUCTION; CHALLENGES; GENERATION; PLATFORMS; SAFETY;

D O I：

10.1128/JVI.01924-17

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Human and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common adenovirus vectors such as Ad5. However, baseline immunity to these vectors still exists in human populations. Traditional cloning of new adenovirus vaccine vectors is a long and cumbersome process that takes 2 months or more and that requires rare unique restriction enzyme sites. Here we describe a novel, restriction enzyme-independent method for rapid cloning of new adenovirus vaccine vectors that reduces the total cloning procedure to 1 week. We developed 14 novel adenovirus vectors from rhesus monkeys that can be grown to high titers and that are immunogenic in mice. All vectors grouped with the unusual adenovirus species G and show extremely low seroprevalence in humans. Rapid cloning of novel adenovirus vectors is a promising approach for the development of new vector platforms. Rhesus adenovirus vectors may prove useful for clinical development. IMPORTANCE To overcome baseline immunity to human and chimpanzee adenovirus vectors, we developed 14 novel adenovirus vectors from rhesus monkeys. These vectors are immunogenic in mice and show extremely low seroprevalence in humans. Rhesus adenovirus vectors may prove useful for clinical development.

引用

页数：11

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