OBJECTIVE: Most HIV-infected individuals develop HIV-specific antibodies (Abs) exhibiting a common idiotype designated as 1F7. Expression of this idiotype establishes idiotypic-driven repertoire freeze, maintaining antibody responses ineffective at controlling autologous contemporaneous viruses. As such, this study investigated the temporal dynamics of 1F7-idiotype expression, as well as the role of this idiotype in the selection of HIV-specific broadly neutralizing antibodies (BnAbs). DESIGN: This study investigated the timing of appearance and persistence of 1F7-idiotypic HIV-specific Abs by screening plasma samples from individuals followed longitudinally starting in primary HIV infection. The expression of 1F7 on HIV-specific BnAbs was also investigated to determine whether their development occurs within the context of 1F7-idiotypic repertoire freeze. METHODS: The 1F7 idiotype was detected on gp120, gp41 and membrane proximal external region (MPER) peptide-specific Abs using an enzyme-linked immunosorbent assay (ELISA). HIV-specific Abs in longitudinal plasma samples from six patients and six BnAbs were tested for the presence of the 1F7 idiotype. RESULTS: The idiotype was expressed on HIV-specific Abs within 3 months of infection, with the magnitude of 1F7 detection increasing with time from infection. The 1F7 idiotype was also expressed on all BnAbs tested. CONCLUSION: These results demonstrate that HIV-specific antibody responses are restricted within the 1F7 idiotype from early infection onwards, and that six well characterized BnAbs developed within the context of 1F7-idiotypic repertoire freeze. Future research should evaluate the necessity of the 1F7 idiotype for broad neutralization, and determine if vaccines should target Abs within or outside this idiotypic space.
OBJECTIVE: Most HIV-infected individuals develop HIV-specific antibodies (Abs) exhibiting a common idiotype designated as 1F7. Expression of this idiotype establishes idiotypic-driven repertoire freeze, maintaining antibody responses ineffective at controlling autologous contemporaneous viruses. As such, this study investigated the temporal dynamics of 1F7-idiotype expression, as well as the role of this idiotype in the selection of HIV-specific broadly neutralizing antibodies (BnAbs). DESIGN: This study investigated the timing of appearance and persistence of 1F7-idiotypic HIV-specific Abs by screening plasma samples from individuals followed longitudinally starting in primary HIV infection. The expression of 1F7 on HIV-specific BnAbs was also investigated to determine whether their development occurs within the context of 1F7-idiotypic repertoire freeze. METHODS: The 1F7 idiotype was detected on gp120, gp41 and membrane proximal external region (MPER) peptide-specific Abs using an enzyme-linked immunosorbent assay (ELISA). HIV-specific Abs in longitudinal plasma samples from six patients and six BnAbs were tested for the presence of the 1F7 idiotype. RESULTS: The idiotype was expressed on HIV-specific Abs within 3 months of infection, with the magnitude of 1F7 detection increasing with time from infection. The 1F7 idiotype was also expressed on all BnAbs tested. CONCLUSION: These results demonstrate that HIV-specific antibody responses are restricted within the 1F7 idiotype from early infection onwards, and that six well characterized BnAbs developed within the context of 1F7-idiotypic repertoire freeze. Future research should evaluate the necessity of the 1F7 idiotype for broad neutralization, and determine if vaccines should target Abs within or outside this idiotypic space.
Authors: Matthew S Parsons; Robert J Center; Jean-Pierre Routy; Danielle Rouleau; Roger Leblanc; Mark A Wainberg; Cécile L Tremblay; Marcel D Zannou; Stephen J Kent; Michael D Grant; Nicole F Bernard Journal: AIDS Res Hum Retroviruses Date: 2013-01-29 Impact factor: 2.205