Ucsf clc genomics workbench8/11/2023 Unfortunately, no effective vaccine is available so far against HIV-1 and the most successful vaccine RV144 provided only 31.2% protection against this deadly microbe. Moreover, induction of both CD4 + and CD8 + cells have proven to be effective against HIV infection. Non-neutralizing antibodies are also seen to be effective against HIV-1 infection but so far no immunological correlates have been found, so the induction of broadly neutralizing antibodies is an important aspect of protection against AIDS. Analysis of these elite controllers demonstrated an abundance of CD4 + and CD8 + cells secreting Th1 promoting interferon-gamma (IFN-ɣ) in these patients. Ī subset of HIV infected patients has the ability to remain asymptomatic and maintain high levels of CD4 + cell count for many years without administration of antiretroviral therapy, known as elite controllers. Out of two types of HIV (HIV-1 and HIV-2), HIV-1 is the most prevalent, and potent, and is considered the main reason for AIDS progression around the globe. Apart from these factors, drug resistance in patients receiving antiretroviral therapy (ART) has also played a major role in the global expansion of HIV infections. The inadequate management of HIV infections has been mainly attributed to the lack of accessibility, expensiveness, and the inability of drugs. The importance of vaccination is highlighted by the present COVID pandemic, where only an effective vaccine has helped significantly reduce the rate of infection rate and decrease COVID-19 related morbidity and mortality. Although these figures were 23% less than those reported in 2010, and besides the availability of many successful drugs such as dolutegravir, efavirenz, and ritonavir, it is still believed that a successful vaccine will be required to eradicate Acquired Immunodeficiency Syndrome (AIDS) (caused by HIV infection) completely from the human population. Graphical AbstractĪn estimated 1.7 million people were infected with the Human Immunodeficiency Virus (HIV) in 2019, and despite the availability of effective treatments, the death toll was 690,000. Our results indicate HIV-1b to be more promising than HIV-1a experimental validations can confirm the efficacy and safety of both constructs and in-vivo efficacy in animal models. TLR-3 docking and in-silico cloning of both constructs were also performed. Both proposed multi-epitope vaccines were found to be antigenic, non-allergenic, stable, and induce cellular, humoral, and innate immune responses. HIV-1a and HIV-1b were subjected to antigenicity, allergenicity, structural quality analysis, immune simulations, and MD (molecular dynamics) simulations. Conserved, antigenic, non-allergenic, T-cell inducing, B-cell inducing, IFN-ɣ inducing, non-human homologous epitopes were selected and combined to propose two vaccine constructs i.e., HIV-1a (without adjuvant) and HIV-1b (with adjuvant). The consensus sequence was generated after alignment and used to predict epitopes. For this, all polyprotein and protein sequences of HIV-1 were retrieved from the LANL (Los Alamos National Laboratory) database. The current study aims to tackle these limitations and propose the desired vaccine utilizing immunoinformatic approaches that have returned promising results in designing vaccines against various rapidly mutating organisms. Unfortunately, vaccine trials so far have returned unfruitful results, possibly due to their inability to induce effective cellular, humoral and innate immune responses. Despite being in the 21 st century, the world has still not been able to vanquish the global AIDS epidemic, and the only foreseeable solution seems to be a safe and effective vaccine.
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