# Immunoinformatic Prediction of HIV-1 Glycoprotein gp120 and Nef Epitopes Conjugated to HBsAg-Binding Protein (SBP) to Induce the Humoral and Cellular Immune Response

## TL;DR

This paper proposes a new HIV-1 vaccine design using computational methods to combine viral epitopes with a protein that boosts immune response.

## Contribution

A novel in silico-designed co-epitope vaccine construct using gp120 and Nef epitopes fused with HBsAg-binding protein (SBP).

## Key findings

- The vaccine construct shows high structural stability and potential for interaction with Toll-like receptors.
- The design enhances both humoral and cellular immune responses by stimulating T and B cells.
- Flexible linkers enable sequential delivery of B cell, HTL, and CTL epitopes for effective antigen presentation.

## Abstract

Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Virus (HIV), and continues to be responsible for a substantial number of deaths worldwide each year. Development of a robust and efficient HIV-1 vaccine remains a critical priority. Structural analysis of viral proteins provides a foundational approach to designing peptide-based immunogenic vaccines. In the current experiment, we used computational prediction approaches alongside molecular docking and molecular dynamics (MD) simulations to identify potential epitopes within gp120 and Nef proteins. The selected co-epitopes were fused with the HBsAg-binding protein (SBP), a 344-amino acid protein previously identified in our laboratory through screening of a human liver cDNA expression library against HBsAg, to facilitate efficient delivery to and uptake by dendritic cells (DCs), thereby enhancing antigen (Ag) presentation. Flexible linkers are used to connect B cells, Helper T Lymphocytes (HTLs), and Cytotoxic T Lymphocytes (CTLs) in a sequential manner. The assembled vaccine construct comprises 757 amino acids, corresponding to a recombinant protein of 83.64 kDa molecular weight. Structural analysis through docking studies, MD simulations, and 3D structure validation revealed that the designed protein exhibits high structural stability and potential for interaction with Toll-like receptors (TLRs). These findings support the vaccine’s ability to enhance cellular and humoral feedback, including the stimulation of T and B cells and induction of antibody (Ab) production. The results underscore the promise of this in silico designed co-epitope vaccine as a viable candidate for HIV-1 prevention and suggest that such constructs may serve as effective immunogens in future HIV-1 vaccine strategies.