همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Applying immunoinformatics methods for Multiepitope Vaccine Design against HIV virus Based on the INT, RT, PRO genes

نویسندگان :

Fatemeh Hassanzadeh¹ Zahra Hassanzadeh² Ava Hashempour³

1- دانشگاه علوم پزشکی شیراز 2- دانشگاه علوم پزشکی شیراز 3- دانشگاه علوم پزشکی شیراز

کلمات کلیدی :

Bioinformatics،AIDS،Vaccine،PRO-RT- INT

چکیده :

Background and Objective Acquired Immunodeficiency Syndrome, which is a symptom of infection with the human immunodeficiency virus, remains one of the challenges in health globally, even with the advancement in antiretroviral therapies. The dominant strain, HIV-1, causes AIDS through the progressive destruction of the immune system, particularly the CD4+ T cells. Current ART drugs, such as dolutegravir and efavirenz, reduce morbidity but are limited by costs, accessibility issues, and rising drug resistance. The promising alternative is the development of a multi-epitope vaccine that is able to induce robust immune responses capable of eradicating the virus from the population. Immunoinformatics approaches have been employed for the identification and prioritization of epitopes with a view to designing such a vaccine. Materials and Methods This study utilizes a systematic immunoinformatics pipeline for the design of a multi-epitope subunit vaccine. Conserved regions in HIV-1 PRO, RT, and INT proteins were identified by using the NCBI CDD-BLAST tool. IEDB and other bioinformatics tools were utilized to predict HTL, CTL, and B-cell epitopes. After prediction, filtering was performed on the basis of antigenicity, allergenicity, toxicity, and human proteome homology. Selected epitopes were connected by means of specific linkers, and the adjuvant 50S ribosomal protein L7/L12 was incorporated for enhanced immunogenicity. The tertiary structure was modelled using I-TASSER and AlphaFold and further refined by GalaxyRefine. Molecular docking with TLRs was done in order to have an interaction potential. Immune simulation study predicted vaccine capacity for strong and long-lasting immune response. Findings This led to the development of a vaccine construct of 553 amino acids, which contained 11 CTL, 8 HTL, and 7 linear B-cell epitopes. The vaccine exhibited high antigenicity-a VaxiJen score of 0.6017-non-toxicity, non-allergenicity, and solubility (QuerySol: 0.622). Refinement of the 3D structure resulted in a high validation score of 95.6% favored Ramachandran plot regions. Stronger interactions in docking studies between the epitopes and TLR-3, TLR-4, TLR-5, TLR-8, and TLR-9 suggested strong activation of innate immunity. The population coverage analysis revealed that more than 99% of the global HLA alleles were covered by the selected epitopes. Immune simulations resulted in significant activation of CD4+, CD8+ T cells, and B cells with high levels of interferon-gamma production. Conclusion The immunoinformatics-designed multi-epitope vaccine represents a new, effective, and economical alternative for HIV-1 vaccination. Targeting conserved regions and experimentally validated epitopes, the construct overcomes several limitations associated with traditional vaccine development. Predicted global population coverage and immune efficacy underscore its potential for clinical trial purposes. Further steps of the process will encompass experimental validation, in vivo testing, and optimization for large-scale production. It thus places computational biology at an important crossroads where centuries-old public health crises, like HIV/AIDS, are being combated with novel vaccine strategies.