مقالات پذیرفته شده در پنجمین کنگره بین المللی زیست پزشکی
HIV Vaccinations
HIV Vaccinations
Saman Hakimian,1Mohammad Shayestehpour,2Shaghayegh Yazdani,3,*
1. M.sc student of Pathogenic Microbes Islamic Azad University Central Tehran Branch 2. Autoimmune Diseases Research Center, Kashan University of Medical Sciences, Kashan, I.R. Iran 3. Department of Microbiology, Faculty of Advanced Science & Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Introduction: Since the first clinical observation of AIDS and the subsequent isolation of the causing retrovirus HIV in the early 1980s, the HIV/AIDS epidemic continues to be one of the major global health threats. In 2019, there were 1.7 million new infections and 690,000 AIDS-related deaths globally. In 2020, 38 million people were living with HIV.
However, the medications are expensive, require strict adherence to dosing regimens for efficacy and cause side effects. Moreover, some HIV- infected individuals develop drug resistance, requiring changes in medications. Most importantly, access to treatment remains a substantial barrier, particularly in low- and medium-income nations, as evidenced by persistently high rates of new infections over the last ten years. Thus, a prophylactic vaccine remains a central component of a multi-pronged strategy to end the epidemy.
Methods: Current HIV vaccine have primarily focused on inducing antibodies that prevent the virus from infecting host cells. Much of the work in this area has been based on protein subunit vaccines, an approach utilizing recombinant viral protein as a target immunogen. The primary roadblocks to HIV bnAb vaccine development include the role of tolerance mechanisms in limiting bnAb B cell precursor development, peripheral anergy and the requirement that bnAbs have very unusual traits to neutralize HIV.
HIV neutralizing antibodies prevent virions from infecting CD4+ cells by directly blocking virion entry and membrane fusion. In contrast, non-neutralizing Envelope (Env) antibodies that bind to virus-infected cells have been postulated to protect, albeit in a less potent manner, through Fc-related effector functions such as antibody-dependent cellular cytotoxicity (ADCC). Indeed, ADCC was one proposed correlate of decreased transmission risk in the RV144 HIV vaccine efficacy trial.
Results: Two ongoing HIV efficacy trials, HVTN 705 and 706 (NCT03060629, NCT03964415), are also testing the hypothesis that non-neutralizing antibodies are protective.
Vaccine-induced CTL responses depend not only on CD8+ T cells but also CD4+ T cells and DCs. For optimal CTL induction, antigenic peptides must first be processed and presented on MHCII by DCs to peptide-specific CD4+ T cells, which bind via T cell receptors (TCRs) and the CD4 co-receptor. In the subsequent exchange of co-stimulatory signals between the CD4+ T cell and DC. The DC becomes “licensed” to activate naïve CD8+ T cells. The CD4+ T cell, on the other hand, responds by proliferating and differentiating into a cytokine-producing effector T helper cell.
Conclusion: Through a process of cross-presentation, DCs present peptides derived from exogenous antigens on MHCI to CD8+ T cells bearing peptide-specific TCRs. Naïve CD8+ T cells that recognize peptide-MHCI complexes require two more signals in order to differentiate into cytotoxic effector cells: CD28 on the T cell interacting with CD80 and CD86 on the DC and IL-2 produced by activated T helper cells, which binds the IL-2 receptor on the primed CD8+ T cell. With these three signals, a peptide-specific CD8+ T cell undergoes rapid clonal expansion and differentiation into effector CTLs, with potent cytotoxic and cytokine-secreting capacity. Following the massive expansion of CTLs, there is a phase of programmed contraction where most effector CTLs undergo apoptosis but leaving behind a small number of memory CTLs. Upon re-encounter of cognate peptide on MHCI, these memory CTLs rapidly proliferate to form a new pool of effector cells to eliminate infected cells A CD8+ T cell-inducing vaccine faces the same challenge as an antibody-inducing vaccine, in that it must contend with tremendous viral diversity.