Human immunodeficiency virus (HIV) is a pathogenic virus capable of entering the human body and replicating within T cells, ultimately leading to acquired immunodeficiency syndrome. In contrast, GB-virus C (GBV-C), a member of the Flaviviridae family, also infects humans but, according to current studies, is not associated with any known pathogenic effects. Unlike most RNA viruses, GBV-C encodes a single polyprotein. It is primarily transmitted through blood and sexual contact. GBV-C comprises three strains: GBV-C, hepatitis G virus (HGV), and other less-studied strains. The HGV strain has been detected in patients with liver cirrhosis; however, there is no evidence that it causes liver disease. Notably, GBV-C reduces immune activation in HIV-infected patients. It has been shown to have a significant effect on the target cell receptors for HIV, indicating its potential as a model for vaccine development against HIV. However, there is a lack of information and studies concerning this virus. GBV-C-based vaccine development faces many challenges, such as concerns about safety and efficacy, limited understanding of its mechanisms of action and immunogenicity, HIV strain variability, ethical and regulatory considerations, production and delivery logistics, long-term outcomes, and public perception and acceptance. Nevertheless, bioinformatic techniques can play a crucial role in overcoming these challenges through approaches such as comparative genomics, epitope mapping, structural bioinformatics, and vaccine design and optimization.