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ISG15

Vaxjo ID 232       
Vaccine Adjuvant Name ISG15       
Adjuvant VO ID VO_0005719
Description A ubiquitin-like protein induced by interferons; acts intracellularly via ISGylation and extracellularly as a cytokine with immunomodulatory effects       
Stage of Development Research       
Host Species for Testing Mouse       
Components IFN induction is the IFN-stimulated gene 15 (ISG15), which encodes a ubiquitin-like protein that undergoes a reversible posttranslational modification (ISGylation).       
Structure Small ubiquitin-like protein; wild-type (ISG15-wt) includes LRLRGG motif for conjugation; mutant (ISG15-mut) has LRLRAA motif preventing ISGylation       
Appearance Constructed as DNA vectors: pCAGGS-ISG15-wt and pCAGGS-ISG15-mut, used intramuscularly at 50 μg per dose       
Storage Plasmid DNA stored and used in endotoxin-free PBS; exact temperature not specified       
Dosage 50 µg DNA-ISG15 (wt or mut) mixed with 50 µg DNA-gp120; followed by 1×10⁷ PFU MVA-B booster       
Function The study clearly highlights the potential use of the IFN-induced ISG15 protein as an immune adjuvant to enhance immune responses to HIV antigens, suggesting that this molecule might be exploitable for prophylactic and therapeutic vaccine approaches against pathogens. IMPORTANCE This study described the potential role of ISG15 as an immunomodulatory molecule in the optimization of HIV/AIDS vaccine candidates. Using a DNA prime-MVA boost immunization protocol, the results indicated an increase in the potency and the quality of the HIV-1 Env-specific CD8 T cell response. These results highlight the adjuvant potency of ISG15 to elicit improved viral antigen presentation to the immune system, resulting in an enhanced HIV-1 vaccine immune response.       
Safety Well tolerated in mice; enhances immune cell infiltration without adverse effects; promotes immunostimulation without toxicity       
References
Gómez et al., 2020: Gómez CE, Perdiguero B, Falqui M, Marín MQ, Bécares M, Sorzano CÓS, García-Arriaza J, Esteban M, Guerra S. Enhancement of HIV-1 Env-Specific CD8 T Cell Responses Using Interferon-Stimulated Gene 15 as an Immune Adjuvant. Journal of virology. 2020; 95(2); . [PubMed: 33115866].