title: 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.
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.
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Carmen Elena
authors.initials: CE
authors.lastname: Gómez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Perdiguero
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Nájera
authors.forename: Carlos Oscar S
authors.initials: CO
authors.lastname: Sorzano
authors.forename: Victoria
authors.initials: V
authors.lastname: Jiménez
authors.forename: Rubén
authors.initials: R
authors.lastname: González-Sanz
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D056704:Adaptive Immunity; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002642:Chick Embryo; D017353:Gene Deletion; D005822:Genetic Vectors / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D000882:Haplorhini; D007156:Immunologic Memory; D007370:Interferon Type I / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; D007370:Interferon Type I; C572770:NYVAC-C vaccine; D007371:Interferon-gamma