An integrated mutation-based immunoinformatic approach incorporating variability in epitopes: A Study Based on HIV Subtype C

Saurav Kumar Mishra ¹ Neeraj Kumar ² Md. Harun Or Rashid ³ Sharifa Sultana ⁴ Turki M Dawoud ⁵ Mohammed Bourhia ^6* Georrge John J ^1*

• ¹ Department of Bioinformatics, University of North Bengal, Darjeeling, West Bengal, India
• ² Bhupal Nobles University, Udaipur, Rajasthan, India
• ³ Macquarie University, Sydney, Sydney, Australia
• ⁴ Daffodil International University, Dhaka, Dhaka, Bangladesh
• ⁵ King Saud University, Riyadh, Riyadh, Saudi Arabia
• ⁶ Université Ibn Zohr, Agadir, Morocco

Currently, HIV (Human Immunodeficiency Virus) infection is one of the leading complications in public health that causes Acquired Immunodeficiency Syndrome (AIDS), especially in the African Region. No specific vaccine is available to combat this due to the multi-strain variability becoming one of the hurdles. In this investigation, we employed the variability in the epitope of the HIV Subtype C targets to introduce mutations and construct an epitope-based vaccine. Four targets were examined to predict the B and T cells (Major Histocompatibility Complex Class I and II). Among the predicted epitopes, immunodominant epitopes were selected and were mapped with the identified variable amino acid to incorporate mutation. These selected and mutated epitopes were used for the non-mutated and mutated vaccine construction, considering linker for fusion and adjuvant to improve the activity. The vaccine's structure was modelled and examined to validate its structural quality, and a high population coverage was also found. The docking investigation of the non-mutated and mutated vaccine with Toll-like Receptor 3 shows remarkable activity followed by strong binding affinity, and the simulation of over 100ns revealed the constancy of the complex system. The immune response revealed its strong effectiveness by generating multiple immunoglobulins followed by the time step of infection, and further, the in silico cloning demonstrated a high expression in Escherichia coli based on their favourable Codon Adaptation Index and GC value. This integrated approach in this investigation will help to plan a potent immunodominant vaccine that can work for multiple strains of HIV infection.