Abstract
The use of an adjuvant in vaccination is thought to be effective for enhancing immune responses to various pathogens. We genetically constructed a live attenuated simian human immunodeficiency virus (SHIV) to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When the macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B had become undetectable, SHIV89.6P was not detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of the pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection.
Highlights
Despite the considerable resources that have been committed to developing an effective human immunodeficiency virus (HIV) vaccine over the past three decades, this objective remains elusive. anti-retroviral therapy has led to a dramatic reduction in HIV-related morbidity and mortality, it is not a cure[1]
We examined immune responses in cynomolgus macaques inoculated with an adjuvant moleculeexpressing virus, simian human immunodeficiency virus (SHIV)-Antigen 85B (Ag85B), and the SHIV-specific immunity induced by SHIV-Ag85B in the macaques after challenge with pathogenic SHIV89.6P
The SHIV-Ag85B-inoculated macaques showed a larger percentage of antigen-specific CD8+ T cells than that in the SHIV-NI-inoculated macaques
Summary
Despite the considerable resources that have been committed to developing an effective human immunodeficiency virus (HIV) vaccine over the past three decades, this objective remains elusive. anti-retroviral therapy has led to a dramatic reduction in HIV-related morbidity and mortality, it is not a cure[1]. Despite the considerable resources that have been committed to developing an effective human immunodeficiency virus (HIV) vaccine over the past three decades, this objective remains elusive. The development of an effective vaccine could prevent the spread of HIV infection, but vaccination efforts have been relatively unsuccessful over the past three decades[4,5]. The live attenuated immunodeficiency viruses nef-deleted simian immunodeficiency virus (SIV) and simian human immunodeficiency virus (SHIV) have proven to be highly effective for vaccines in non-human primate models, but they are not sufficiently safe to use as a template for HIV vaccines in humans[12,13,14]. Several studies have demonstrated that insertion of a cytokine or chemokine gene in live attenuated and genetically defective SIV or SHIV can improve the immunogenicity and enhance the protective capacity of the virus[15,16,17] compared to those of safer, less virulent strains
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
