Construction and properties of a herpes simplex virus 2 dl5-29 vaccine candidate strain encoding an HSV-1 virion host shutoff protein.

Vaccine
Natalia J ReszkaD M Knipe

Abstract

The replication-defective herpes simplex virus 2 (HSV-2) dl5-29 mutant virus strain with deletions in the U(L)5 and U(L)29 genes has been shown to protect mice and guinea pigs against challenge with wild-type (wt) HSV-2 and to protect against ocular disease caused by HSV-1 infection. The dl5-29 strain is currently being prepared for clinical trials as a herpes vaccine candidate. As a possible approach to improve the efficacy of dl5-29 as a genital herpes vaccine, we replaced the U(L)41 gene encoding the virion host shutoff function (vhs) with the U(L)41 gene from HSV-1. While the HSV-2 U(L)41 and HSV-1 U(L)41 gene products have analogous functions, vhs-1 is 40-fold less active than vhs-2. Previously, it was shown that disruption of the U(L)41 gene can increase the efficacy of dl5-29 as a vaccine against HSV-2. These properties led us to hypothesize that replacement of vhs-2 by vhs-1 would decrease cytopathic effects in infected host cells, allowing longer survival of antigen-presenting cells and induction of stronger immune responses. The new recombinant dl5-29-41.1 virus shows nearly the same immunogenicity and protection against HSV-2 challenge as the parental dl5-29 virus or a triply deleted mutant virus, dl5-29-41, in the m...Continue Reading

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Citations

Jun 16, 2012·Future Virology·Xavier DervillezLbachir Benmohamed
Apr 23, 2013·Clinical & Developmental Immunology·Soren Gantt, William J Muller
Feb 9, 2011·Immunology and Cell Biology·Daniëlle HorstEmmanuel J H J Wiertz
Mar 8, 2012·Reviews in Medical Virology·Erin Chung, Jonathan Sen
Apr 27, 2016·Current Clinical Microbiology Reports·Brent Stanfield, Konstantin Gus Kousoulas
Feb 28, 2013·Human Vaccines & Immunotherapeutics·Jeffrey L Coleman, Deepak Shukla
May 15, 2013·Current Opinion in Virology·Werner J D OuwendijkDavid M Koelle
May 20, 2014·Expert Review of Vaccines·William P Halford
Jun 6, 2014·Expert Opinion on Drug Delivery·Shun ChenWeien Yuan
Aug 1, 2014·Expert Review of Vaccines·Shane C McAllister, Mark R Schleiss

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