In order to develop new vaccination strategies able to enhance the cellular immunity towards Tat as well as other HIV-1 proteins, a large number of viral vectors expressing HIV-1 or SIV-1 antigens are under investigation. Many of these viral vectors have been reported for their capacity to induce strong in vivo Th1 and CTL responses, as well as high antibody titers, against various HIV-1 gene products. Herpes simplex type-1 virus (HSV-1)-based vectors show several advantages for prophylaxis against viral infections. They have been shown: i) to elicit strong and durable antigen-specific immune responses by various routes of inoculation; ii) the viral DNA persists inside the host’s cell nucleus as an episomal element, thus eliminating the safety concerns deriving from the random integration of the viral genome into the host’s DNA; iii) they carry the tk gene, encoding the viral thymidine kinase, that, in case of undesired effects, can be used, in combination with specific antiviral drugs, to kill the virus-harboring cells. The overall scientific goal of this project is to contribute to a better understanding of the immune biology of HIV infection using a novel generation of gene transfer vectors, as a first step towards the development of innovative genetic vaccines to fight against HIV and HSV pathogens. To this end, we will develop herpes simplex virus type 1 (HSV-1)-based vectors for the generation and analysis of HIV-specific vaccines. Our approach is based on the possibility of engineering HSV-1-based vectors expressing and/or displaying HIV antigens. We will modify HSV recombinant vectors to express HIV genes for endogenous expression in transduced cells (MHC-I) and to display Env and/or Gag antigens f on the surface of the HSV virions (MHC-II), to promote Ag association to class I and/or class II major histocompatibility complex (MHC), either individually or in combination, alone or together with immune-modulator genes. Our purpose is to evaluate the ability of these vectors to elicit protective immune responses against HIV infection in immunocompetent mice, therefore helping to elucidate the contribution of individual HIV antigens, and of different components of the immune system, to the architecture of the immune response and to protection against HSV wild type virus and other challenge agents. The use of defective HSV-1 vectors vaccines will permit the investigation of different routes and protocols of immunization.
Preparation of non-replicating HSV-1 viral vectors expressing HIV Tat and/or displaying other HIV proteins for systemic and mucosal immunization as an anti-HIV vaccination approach
MARCONI, Peggy Carla Raffaella
2007
Abstract
In order to develop new vaccination strategies able to enhance the cellular immunity towards Tat as well as other HIV-1 proteins, a large number of viral vectors expressing HIV-1 or SIV-1 antigens are under investigation. Many of these viral vectors have been reported for their capacity to induce strong in vivo Th1 and CTL responses, as well as high antibody titers, against various HIV-1 gene products. Herpes simplex type-1 virus (HSV-1)-based vectors show several advantages for prophylaxis against viral infections. They have been shown: i) to elicit strong and durable antigen-specific immune responses by various routes of inoculation; ii) the viral DNA persists inside the host’s cell nucleus as an episomal element, thus eliminating the safety concerns deriving from the random integration of the viral genome into the host’s DNA; iii) they carry the tk gene, encoding the viral thymidine kinase, that, in case of undesired effects, can be used, in combination with specific antiviral drugs, to kill the virus-harboring cells. The overall scientific goal of this project is to contribute to a better understanding of the immune biology of HIV infection using a novel generation of gene transfer vectors, as a first step towards the development of innovative genetic vaccines to fight against HIV and HSV pathogens. To this end, we will develop herpes simplex virus type 1 (HSV-1)-based vectors for the generation and analysis of HIV-specific vaccines. Our approach is based on the possibility of engineering HSV-1-based vectors expressing and/or displaying HIV antigens. We will modify HSV recombinant vectors to express HIV genes for endogenous expression in transduced cells (MHC-I) and to display Env and/or Gag antigens f on the surface of the HSV virions (MHC-II), to promote Ag association to class I and/or class II major histocompatibility complex (MHC), either individually or in combination, alone or together with immune-modulator genes. Our purpose is to evaluate the ability of these vectors to elicit protective immune responses against HIV infection in immunocompetent mice, therefore helping to elucidate the contribution of individual HIV antigens, and of different components of the immune system, to the architecture of the immune response and to protection against HSV wild type virus and other challenge agents. The use of defective HSV-1 vectors vaccines will permit the investigation of different routes and protocols of immunization.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
