title: Insertion of vaccinia virus C7L host range gene into NYVAC-B genome potentiates immune responses against HIV-1 antigens.
abstract: BACKGROUND
  The highly attenuated vaccinia virus strain NYVAC expressing HIV-1 components has been evaluated as a vaccine candidate in preclinical and clinical trials with encouraging results. We have previously described that the presence of C7L in the NYVAC genome prevents the induction of apoptosis and renders the vector capable of replication in human and murine cell lines while maintaining an attenuated phenotype in mice.
  
  
  RESULTS
  In an effort to improve the immunogenicity of NYVAC, we have developed a novel poxvirus vector by inserting the VACV host-range C7L gene into the genome of NYVAC-B, a recombinant virus that expresses four HIV-1 antigens from clade B (Env, Gag, Pol and Nef) (referred as NYVAC-B-C7L). In the present study, we have compared the in vitro and in vivo behavior of NYVAC-B and NYVAC-B-C7L. In cultured cells, NYVAC-B-C7L expresses higher levels of heterologous antigen than NYVAC-B as determined by Western blot and fluorescent-activated cell sorting to score Gag expressing cells. In a DNA prime/poxvirus boost approach with BALB/c mice, both recombinants elicited robust, broad and multifunctional antigen-specific T-cell responses to the HIV-1 immunogens expressed from the vectors. However, the use of NYVAC-B-C7L as booster significantly enhanced the magnitude of the T cell responses, and induced a more balanced cellular immune response to the HIV-1 antigens in comparison to that elicited in animals boosted with NYVAC-B.
  
  
  CONCLUSIONS
  These findings demonstrate the possibility to enhance the immunogenicity of the highly attenuated NYVAC vector by the insertion of the host-range gene C7L and suggest the use of this modified vector as an improved vaccine candidate against HIV/AIDS.
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, CSIC, Ciudad Universitaria Cantoblanco, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Nájera
authors.forename: Carmen Elena
authors.initials: CE
authors.lastname: Gómez
authors.forename: Juan
authors.initials: J
authors.lastname: García-Arriaza
authors.forename: Carlos Oscar
authors.initials: CO
authors.lastname: Sorzano
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D005822:Genetic Vectors; D016679:Genome, Viral; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014616:Vaccinia virus / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D015488:HIV Antigens