Antibodies (Abs) specific to the HIV-1 envelope regions, the CD4 binding site (CD4bs), V3 and V2 loops display neutralizing activity and may have protective functions. These Abs are present in almost all HIV-infected subjects and can also be induced by vaccines, as shown in clinical trials, but exhibit rather low neutralizing activities. To determine a threshold of mutations which may represent the maturity needed for cross-neutralizing antibodies, we have studied the percentage of mutations in the variable fragment of the heavy and light chain genes of 63 human monoclonal Abs (mAbs) which are specific to CD4bs, V3 and V2 domains, and tested their neutralizing activities against a panel of 41 pseudoviruses (psVs). All 63 mAbs neutralized, with various frequencies, a panel of sensitive Tier 1 psVs while the more resistant Tier 2 psVs were neutralized sporadically and only by V3 mAbs. Mutation frequencies ranged from 2.4% to 16.7% of the nucleotide sequences were observed for both the heavy and light chain genes of all mAbs. The percentage of mutations was comparable for CD4bs, V3 and V2 mAbs and had no correlation with the breadth of neutralization. The results indicate that mAbs with at least a few percent of mutations can neutralize sensitive Tier 1 viruses, which probably can be achieved during HIV vaccination.
- Copyright © 2013 by The American Association of Immunologists, Inc.