Document Type


Publication Date



Reverse Vaccinology, Intrinsically Disordered Protein, Antibody, Antigen, Structural Flexibility

Digital Object Identifier (DOI)


The absence of advancement in finding efficient vaccines for several human viruses, such as hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and herpes simplex viruses (HSVs) despite 30, 40, and even 60 years of research, respectively, is unnerving. Among objective reasons for such failure are the highly glycosylated nature of proteins used as primary vaccine targets against these viruses and the presence of neotopes and cryptotopes, as well as high mutation rates of the RNA viruses HCV and HIV-1 and the capability to establish latency by HSVs. However, the lack of success in utilization of the structure-based reverse vaccinology for these viruses is likely to be related to the presence of highly flexible and intrinsically disordered regions in human antibodies (Abs) and the major immunogens of HIV-1, HCV, and HSVs, their surface glycoproteins. This clearly calls for moving from the rational structure-based vaccinology to the unstructural vaccinology based on the utilization of tools designed for the analysis of disordered and flexible proteins, while looking at intrinsically disordered viral antigens and their interactions with intrinsically disordered/flexible Abs.

Rights Information

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Was this content written or created while at USF?


Citation / Publisher Attribution

Exploration of Immunology, v. 2, p. 731-748