Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity

Nature
Diane M RobertsDan H Barouch

Abstract

A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world. Here we show that rAd5 vectors can be engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5 vectors in which the seven short hypervariable regions (HVRs) on the surface of the Ad5 hexon protein were replaced with the corresponding HVRs from the rare adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high titres and were stable through serial passages in vitro. HVR-chimaeric rAd5 vectors expressing simian immunodeficiency virus Gag proved comparably immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In th...Continue Reading

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Citations

Sep 29, 2009·Biotechnology Letters·Yue-Jun FuAi-Hua Liang
Jan 27, 2007·Current Infectious Disease Reports·Anna R Thorner, Dan H Barouch
Sep 11, 2012·Immunologic Research·Kalani HalemanoMario L Santiago
Sep 11, 2007·Molecular Biotechnology·Joanne T Douglas
Jun 19, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Frédéric VigantKarim Benihoud
Apr 25, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Dan H Barouch
Jun 11, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marcio O Lasaro, Hildegund C J Ertl
May 26, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tanner S MiestRoberto Cattaneo
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Feb 23, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Arturo Reyes-SandovalAdrian V S Hill
Oct 4, 2008·Nature·Dan H Barouch
Dec 3, 2013·Nature Nanotechnology·Che-Ming J HuLiangfang Zhang
Nov 25, 2006·Nature Reviews. Immunology·Norman L Letvin
Jul 12, 2008·Nature Reviews. Immunology·Philip J R Goulder, David I Watkins
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Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Gilad OfekPeter D Kwong
May 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Dan H BarouchJohn P Moore
Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Birgit DreierAndreas Plückthun
Jan 16, 2008·The Journal of Experimental Medicine·Rafick-Pierre Sekaly
Sep 16, 2006·Human Gene Therapy·Delphine Lechardeur, Gergely L Lukacs
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Oct 6, 2006·Journal of Clinical Microbiology·Anna R ThornerDan H Barouch

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