Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways.
An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC) poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. We therefore analysed the HIV immune advantage of NYVAC after removing viral genes that act on several signalling pathways (Toll-like receptors-TLR-interferon, cytokines/chemokines), as well as genes of unknown immune function. We generated a series of NYVAC deletion mutants and studied immune behaviour (T and B cell) to HIV antigens and to the NYVAC vector in mice. Our results showed that combined deletion of selected vaccinia virus (VACV) genes is a valuable strategy for improving the immunogenicity of NYVAC-based vaccine candidates. These immune responses were differentially modulated, positive or negative, depending on the combination of gene deletions. The deletions also led to enhanced antigen- or vector-specific cellular and humoral responses. These findings will facilitate the development of optimal NYVAC-based vaccines for HIV and other diseases.
['Gómez|Carmen Elena|CE|', 'Perdiguero|Beatriz|B|', 'Sánchez-Corzo|Cristina|C|', 'Sorzano|Carlos Oscar S|COS|', 'Esteban|Mariano|M|']
D016915:AIDS Vaccines D000818:Animals D002478:Cells, Cultured D002642:Chick Embryo D016207:Cytokines D005260:Female D005822:Genetic Vectors D015483:HIV Antibodies D015488:HIV Antigens D015699:HIV Envelope Protein gp120 D015658:HIV Infections D015497:HIV-1 D051379:Mice D008807:Mice, Inbred BALB C D017384:Sequence Deletion D015398:Signal Transduction D051193:Toll-Like Receptors D014616:Vaccinia virus D014764:Viral Proteins
HIV-1 NYVAC immunogenicity cytokines/chemokines T and B cell immune response Toll-like receptor immunomodulators interferon