Deficient synthesis of class-switched, HIV-neutralizing antibodies to the CD4 binding site and correction by electrophilic gp120 immunogen.

ABSTRACT:

Objective

HIV is vulnerable to antibodies that recognize a linear CD4 binding site epitope of gp120 (C), but inducing C-directed antibody synthesis by traditional vaccine principles is difficult. We wished to understand the basis for deficient C-directed antibody synthesis and validate correction of the deficiency by an electrophilic gp120 analog (E-gp120) immunogen that binds B-cell receptors covalently.

Methods

Serum antibody responses to a C peptide and full-length gp120 epitopes induced by HIV infection in humans and immunization of mice with gp120 or E-gp120 were monitored. HIV neutralization by monoclonal and variable domain-swapped antibodies was determined from tissue culture and humanized mouse infection assays.

Results

We describe deficient C-directed IgG bu

SUBMITTER: Planque SA 

PROVIDER: S-EPMC4573643 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature