Designing a multi-epitope vaccine targeting the HIV-1 subtype CRF01_AE in Indonesia

HIV has markedly affected millions of people globally, with antiretroviral therapy (ART) transforming acquired immunodeficiency syndrome from a fatal disease to a manageable chronic condition. However, global disparities in ART access persist, particularly in low- and middle-income countries, highlighting the urgent need for affordable HIV vaccines. In this study, we investigated the potential development of a multi-epitope vaccine (MEV) targeting the HIV subtype CRF01_AE, which is prevalent in Indonesia. Using likelihood-based evolutionary inference based on site rates to analyze mutation rates, we identified the Pol and Env proteins as optimal targets. Nine T cell epitopes (five cytotoxic and four helper) were selected based on HLA binding affinity, conservation, antigenicity, and predicted immunogenicity, achieving broad population coverage (∼95 % globally and 99.58 % in Indonesia). The MEV construct incorporated epitopes conjugated to a Vibrio cholerae toxin B subunit adjuvant and a B cell epitope known to induce broadly neutralizing antibodies. In silico characterization, including physicochemical analysis, structural modeling (validated using ProSA-web and Ramachandran plot analysis), and protein-protein docking simulations (using HADDOCK and PRODIGY), demonstrated favorable properties, stable conformation, and high-affinity interaction with antibody fragments (ΔGbind = −10.8 kcal/mol). Molecular dynamics simulations confirmed the formation of a stable complex. Immunogenicity tests revealed a strong antibody and cytokine response. These findings suggest that this MEV construct is a promising and affordable HIV-1 vaccine candidate that warrants further validation.