Animal models allow to compare the efficacy of various vaccine types in the same experimental system, as well as to optimize the vaccine formulations and protocols and select those with the best safety, immunogenicity and efficacy performance. The progress in AIDS research has been hampered by the lack of a small and practical animal model susceptible to HIV infection, suitable for a rapid testing of antiviral compounds and vaccines. This project will be devoted to the establishment of small animal models amenable to assess the efficacy of the vaccine candidates and, in particular, of all HIV antigens. This approach would be extremely useful since mice are relatively inexpensive, largely available, can be used in a larger number in order to obtain statistically significant results, and duration of the experimentation can be greatly reduced. This innovative approach will permit the evaluation of those candidates that cannot be tested in monkeys due to the lack of suitable SHIV models. A new challenge model for mouse based on the use of Herpes simplex virus (HSV) will be developed and used for efficacy studies of vaccine formulations to select rapidly those that will be tested for efficacy in the monkey model. Human infection by HSV causes a variety of diseases ranging from mild cutaneous lesions to life-threatening encephalitis. HSV type 1 (HSV-1) infection is typically associated with orofacial lesions and encephalitis, while HSV type 2 (HSV-2) generally infects the genital region. Mice are susceptible to both HSV-1, HSV-2 and this characteristic make HSV suitable candidate for development of challenge model for efficacy studies of HIV-1 candidate. HSV are manipulated in such a way that they can carry HIV genes in a non-essential locus preserving their ability to give a lytic infection. In the mouse model the challenge with a lethal dose of HSV will be characterized by the progressive onset of vaginal lesions followed by neurological disease and death. In the vaccinated animals the mean composite disease scores of genital lesions, neurological deficits and survival data will be determined daily after infection and will determine the efficacy of the vaccine protocol.
HSV recombinant vectors expressing the HIV-1 antigens to be used as mice efficacy model to select vaccine candidates
MARCONI, Peggy Carla Raffaella
2007
Abstract
Animal models allow to compare the efficacy of various vaccine types in the same experimental system, as well as to optimize the vaccine formulations and protocols and select those with the best safety, immunogenicity and efficacy performance. The progress in AIDS research has been hampered by the lack of a small and practical animal model susceptible to HIV infection, suitable for a rapid testing of antiviral compounds and vaccines. This project will be devoted to the establishment of small animal models amenable to assess the efficacy of the vaccine candidates and, in particular, of all HIV antigens. This approach would be extremely useful since mice are relatively inexpensive, largely available, can be used in a larger number in order to obtain statistically significant results, and duration of the experimentation can be greatly reduced. This innovative approach will permit the evaluation of those candidates that cannot be tested in monkeys due to the lack of suitable SHIV models. A new challenge model for mouse based on the use of Herpes simplex virus (HSV) will be developed and used for efficacy studies of vaccine formulations to select rapidly those that will be tested for efficacy in the monkey model. Human infection by HSV causes a variety of diseases ranging from mild cutaneous lesions to life-threatening encephalitis. HSV type 1 (HSV-1) infection is typically associated with orofacial lesions and encephalitis, while HSV type 2 (HSV-2) generally infects the genital region. Mice are susceptible to both HSV-1, HSV-2 and this characteristic make HSV suitable candidate for development of challenge model for efficacy studies of HIV-1 candidate. HSV are manipulated in such a way that they can carry HIV genes in a non-essential locus preserving their ability to give a lytic infection. In the mouse model the challenge with a lethal dose of HSV will be characterized by the progressive onset of vaginal lesions followed by neurological disease and death. In the vaccinated animals the mean composite disease scores of genital lesions, neurological deficits and survival data will be determined daily after infection and will determine the efficacy of the vaccine protocol.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
