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Improved safety of a replication-competent poxvirus-based HIV vaccine with the introduction of the HSV-TK/GCV suicide gene system.

Abstract：

INTRODUCTION:Replication-competent vaccinia viruses (VACVs) show prolonged antigen expression time and greater stimulation of immune responses than their replication-incompetent counterparts. However, there is the potential risk of serious post-vaccination complications, especially for children and immunocompromised individuals, leading to safety concerns about the reintroduction of VACV as a vaccine vector. In this study, we improved the safety of the vaccinia virus TianTan (VACV-TT) based HIV vaccine by introducing the HSV-TK/GCV suicide gene system, which is composed of the herpes simplex virus type 1 thymidine kinase gene (HSV-tk) and the antiviral drug ganciclovir (GCV). MATERIALS AND METHODS:By inserting the HSV-tk gene into the replication-competent VACV-TT genome, a new vector, TT-TK (VACV-TT expressing the HSV-tk gene), and a candidate vaccine, TT-EnvTK (TT-TK expressing the HIV-1 env gene), were constructed. RESULTS:The new vector TT-TK exhibited reduced replication capacity both in vitro and in vivo in the presence of GCV. GCV inhibited the replication of TT-TK in the brains of mice and skin of rabbits, and provided 100% protection in mice against lethal challenge with TT-TK at a dose of 80mg/kg/day. Furthermore, the candidate vaccine TT-EnvTK induced cellular and humoral immunity against HIV-1 antigen that was comparable to the immunity induced by VTKgpe (VACV-TT expressing HIV-1 env, gag, and pol genes). DISCUSSION:These promising results suggest a new strategy to mitigate the potential risk of post-vaccination complications from replication-competent VACV-based HIV vaccines.

journal_name

Vaccine

journal_title

Vaccine

authors

Zhang Q,Liu Z,Hou J,Wang S,Liu C,Wei M,Liu Y,Shao Y

doi

10.1016/j.vaccine.2016.05.012

subject

Has Abstract

pub_date

2016-06-24 00:00:00

pages

3447-53

issue

30

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(16)30295-X

journal_volume

34

pub_type

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