Abstract
In this review, we trace the concept and potential functional role of regulatory idiotypes in the immune response to human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus, and hepatitis C virus (HCV). A major idiotype involved in these viral infections is recognized and defined by a murine monoclonal antibody (1F7). Antibodies expressing the idiotype defined by 1F7 are dominant in HIV-1 infection and are also found on many broadly neutralizing antibodies against HIV-1. This regulatory idiotypic axis offers opportunities for exploitation in vaccine development for HIV-1, HCV, and other chronic viral infections.
Highlights
Form of clonal dominance that appears to restrict development of neutralizing antibodies against contemporaneous infecting strains of HIV-1 and imposes a trajectory toward chronic infection with HCV
BnAbs that develop against HIV-1 do bear the 1F7 idiotype, indicating that the same idiotypic axis accommodating clonal dominance and original antigenic sin accommodates antibody evolution toward the highly mutated progeny capable of neutralizing diverse strains of HIV1
Learning how to exploit this axis selectively to prime for the development of BnAbs in advance of viral exposure may be a key to more effective vaccination against chronic viruses, such as HIV-1, HCV, and others
Summary
Given the occurrence of repertoire freeze during HIV-1 infection, Parsons et al hypothesized that BnAbs develop from 1F7-idiotypic antibodies established during early infection through multiple rounds of selection and somatic hypermutation [51] To assess this possibility, they screened serial plasma samples from six HIV-infected donors over time points ranging from acute through chronic infection to determine if 1F7-idiotypic antibodies arise during acute infection and are sustained throughout infection. Haynes et al hypothesized that BnAbs might be inducible through vaccination strategies that sequentially expose vaccine recipients to HIV-1 envelope antigens selected on the basis of binding to chronologically relevant antibody isolates, derived from HIV-1-infected donors that developed BnAbs [59] This vaccination strategy might benefit from inclusion of a prime and/or boost with F(ab) of the murine monoclonal anti-idiotypic antibody used to detect the 1F7 idiotype in in vitro assays.
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