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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.
- Source :
-
Vaccine . Jun2016, Vol. 34 Issue 30, p3447-3453. 7p. - Publication Year :
- 2016
-
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 80 mg/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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *POXVIRUS diseases
*AIDS vaccines
*IMMUNE response
*ANTIVIRAL agents
*GANCICLOVIR
Subjects
Details
- Language :
- English
- ISSN :
- 0264410X
- Volume :
- 34
- Issue :
- 30
- Database :
- Academic Search Index
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 116158575
- Full Text :
- https://doi.org/10.1016/j.vaccine.2016.05.012