On the Irrationality of Rational Design of an HIV Vaccine in Light of Protein Intrinsic Disorder

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The lack of progress in finding an efficient vaccine for a human immunodeficiency virus (HIV) is daunting. In fact, this search has spanned nearly four decades without much success. There are several objective reasons for such a failure, which include the highly glycosylated nature of HIV-1, the presence of neotopes, and high mutation rates. This article argues that the presence of highly flexible and intrinsically disordered regions in both human anti-HIV-1 antibodies and the major HIV-1immunogen, its surface glycoprotein gp120, represent one of the major causes for the lack of success in utilization of structure-based reverse vaccinology.

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Archives of Virology, v. 166, p. 1283-1296