Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , VIH-1/inmunología , Humanos , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Carga ViralAsunto(s)
Humanos , Animales , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , VIH-1/inmunología , Carga Viral , Modelos Animales de Enfermedad , Animales Recién NacidosRESUMEN
The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env) glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5) expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.
Asunto(s)
Animales , Humanos , Vacunas contra el SIDA/inmunología , Anticuerpos Antivirales/inmunología , VIH , Infecciones por VIH/prevención & control , Carga Viral/inmunología , Infecciones por VIH/inmunología , Macaca mulatta , Vacunas contra el SIDAS/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunologíaRESUMEN
The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env) glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5) expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.
Asunto(s)
Vacunas contra el SIDA/inmunología , Anticuerpos Antivirales/inmunología , Infecciones por VIH/prevención & control , VIH/inmunología , Carga Viral/inmunología , Animales , Infecciones por VIH/inmunología , Humanos , Macaca mulatta , Vacunas contra el SIDAS/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunologíaRESUMEN
VEE replicon particles (VRP), non-propagating vaccine vectors derived from Venezuelan equine encephalitis virus (VEE), were engineered to express immunogens from the cloned isolate SIVsmH-4, combined in a vaccine cocktail and inoculated subcutaneously to immunize rhesus macaques. The virulent, uncloned challenge stock, SIVsmE660, represented a type of heterologous challenge and the intrarectal challenge modeled infection across a mucosal surface. Prechallenge neutralizing antibodies against SIVsmH-4 were induced in all vaccinates, and a prechallenge cellular immune response could be detected in one of six. Post-challenge, virus loads were reduced at the peak, at set point and at termination (41 weeks post-challenge), although these differences did not reach statistical significance. Significantly elevated levels of CD4+ T cells were observed post-challenge. A strong correlation was noted between a net increase in CD4+ T cell count and lowered virus load at set point.
Asunto(s)
Virus de la Encefalitis Equina Venezolana/genética , Vacunas contra el SIDAS/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/sangre , Recuento de Linfocito CD4 , Modelos Animales de Enfermedad , Vectores Genéticos , Inmunidad Celular , Inyecciones Subcutáneas , Macaca mulatta , Pruebas de Neutralización , Replicón/genética , Vacunas contra el SIDAS/administración & dosificación , Vacunas contra el SIDAS/genética , Linfocitos T Citotóxicos/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Carga Viral , Vacunas Virales/administración & dosificación , Vacunas Virales/genéticaRESUMEN
Infection of the rhesus monkey (Macaca mulatta) with retroviruses originating from African non human primates (SIV) induces in this species an acquired immunodeficiency syndrome (SAIDS) closely resembling AIDS in humans. Analogies between the SIV-rhesus system and AIDS in humans are described in this work, analyzing the close relationship existing between the HIV and SIV viruses, and the similarities between SIV disease in the rhesus and HIV disease in humans. A review of current advances in AIDS vaccine research, using the SIV-rhesus model, is also included.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Síndrome de Inmunodeficiencia Adquirida del Simio , Síndrome de Inmunodeficiencia Adquirida/microbiología , Animales , Modelos Animales de Enfermedad , VIH/genética , Humanos , Macaca mulatta , Síndrome de Inmunodeficiencia Adquirida del Simio/microbiología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios , VacunasRESUMEN
Infection of the rhesus monkey (Macaca mulatta) with retroviruses originating from African non human primates (SIV) induces in this species an acquired immunodeficiency syndrome (SAIDS) closely resembling AIDS in humans. Analogies between the SIV-rhesus system and AIDS in humans are described in this work, analyzing the close relationship existing between the HIV and SIV viruses, and the similarities between SIV disease in the rhesus and HIV disease in humans. A review of current advances in AIDS vaccine research, using the SIV-rhesus model, is also included