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Removal of vaccinia virus genes that block interferon type I and II pathways improves adaptive and memory responses of the HIV/AIDS vaccine candidate NYVAC-C in mice.
- Source :
-
Journal of virology [J Virol] 2012 May; Vol. 86 (9), pp. 5026-38. Date of Electronic Publication: 2012 Mar 14. - Publication Year :
- 2012
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Abstract
- Poxviruses encode multiple inhibitors of the interferon (IFN) system, acting at different levels and blocking the induction of host defense mechanisms. Two viral gene products, B19 and B8, have been shown to act as decoy receptors of type I and type II IFNs, blocking the binding of IFN to its receptor. Since IFN plays a major role in innate immune responses, in this investigation we asked to what extent the viral inhibitors of the IFN system impact the capacity of poxvirus vectors to activate immune responses. This was tested in a mouse model with single and double deletion mutants of the vaccine candidate NYVAC-C, which expresses the HIV-1 Env, Gag, Pol, and Nef antigens. When deleted individually or in double, the type I (B19) and type II (B8) IFN binding proteins were not required for virus replication in cultured cells. Studies of immune responses in mice after DNA prime/NYVAC boost revealed that deletion of B8R and/or B19R genes improved the magnitude and quality of HIV-1-specific CD8(+) T cell adaptive immune responses and impacted their memory phase, changing the contraction, the memory differentiation, the effect magnitude, and the functionality profile. For B cell responses, deletion of the viral gene B8R and/or B19R had no effect on antibody levels to HIV-1 Env. These findings revealed that single or double deletion of viral factors (B8 and B19) targeting the IFN pathway is a useful approach in the design of improved poxvirus-based vaccines.
- Subjects :
- AIDS Vaccines genetics
Animals
CD8-Positive T-Lymphocytes immunology
Chick Embryo
Gene Deletion
Genetic Vectors immunology
HIV Envelope Protein gp120 genetics
HIV Envelope Protein gp120 immunology
HIV Infections immunology
HIV Infections prevention & control
HIV-1 genetics
HIV-1 immunology
Haplorhini
Mice
Mice, Inbred BALB C
Signal Transduction immunology
T-Lymphocytes immunology
Vaccinia virus genetics
Vaccinia virus immunology
AIDS Vaccines immunology
Adaptive Immunity
Immunologic Memory
Interferon Type I metabolism
Interferon-gamma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 86
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 22419805
- Full Text :
- https://doi.org/10.1128/JVI.06684-11