Abstract
We recently reported the induction of potent, cross-clade neutralizing antibodies (nAbs) against Human Immunodeficiency Virus type-1 (HIV-1) in rabbits using gp120 based on an M-group consensus sequence. To better characterize these antibodies, 93 hybridomas were generated, which represent the largest panel of monoclonal antibodies (mAbs) ever generated from a vaccinated rabbit. The single most frequently recognized epitope of the isolated mAbs was at the very C-terminal end of the protein (APTKAKRRVVEREKR), followed by the V3 loop. A total of seven anti-V3 loop mAbs were isolated, two of which (10A3 and 10A37) exhibited neutralizing activity. In contrast to 10A3 and most other anti-V3 loop nAbs, 10A37 was atypical with its epitope positioned more towards the C-terminal half of the loop. To our knowledge, 10A37 is the most potent and broadly neutralizing anti-V3 loop mAb induced by vaccination. Interestingly, all seven anti-V3 loop mAbs competed with PGT121, suggesting a possibility that early induction of potent anti-V3 loop antibodies could prevent induction of more broadly neutralizing PGT121-like antibodies that target the conserved base of the V3 loop stem.
Highlights
A critical problem for developing a vaccine against human immunodeficiency virus type 1 (HIV-1) is the difficulty in inducing broadly neutralizing antibodies against the large number of viral variants that exist [1,2,3]
Antibody competition analyses indicated that antibodies that could compete with bnAbs VRC01 and PGT121 in binding gp120 were maintained (Fig 1D), albeit at a slightly lower level compared to the level observed after the fifth immunization [43]. These results indicated that despite slight reductions in neutralizing activity and antibody levels that compete with bnAbs, the overall quality of antibody responses remained largely unchanged despite a prolonged resting period
As an initial attempt to define epitopes recognized by what we believe is the largest panel of anti-gp120 rabbit monoclonal antibodies (mAbs) generated to date, we examined antibody reactivity against different protein constructs and some of the immunogenic peptides identified from overlapping peptide ELISA [43]
Summary
A critical problem for developing a vaccine against human immunodeficiency virus type 1 (HIV-1) is the difficulty in inducing broadly neutralizing antibodies (bnAb) against the large number of viral variants that exist [1,2,3]. The envelope glycoproteins gp120 and gp are the sole HIV-1 antigens on the virion surface targeted by nAbs. characterizing the immunogenic and structural features of the HIV-1 envelope is important for designing immunogens to elicit bnAbs and to understand the humoral response to HIV-1 infection [4,5,6]. June 3, 2015 not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
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