Existing HIV-1 immunogens are unable to elicit broadly reactive neutralizing antibodies (NAb) that are likely necessary for an optimally effective vaccine. Rare neutralizing monoclonal antibodies (mAbs) targeting the envelope glycoprotein exist and uncommon sera from HIV-1-infected individuals can neutralize diverse HIV-1 strains. From a well characterized patient cohort, we identified several sera displaying potent and broad HIV-1 neutralization and mapped the neutralizing specificity in the two broadest sera. Adsorption with gp120 derived from a single clade B isolate diminished serum neutralizing activity against cross-clade viral strains. A gp120 CD4 binding defective point mutant displayed substantially reduced adsorption capacity. For both sera, selective antibody elution and adsorption revealed a fraction of antibodies directed against the CD4 receptor binding site (CD4bs) that were able to neutralize diverse HIV-1 strains. Previously unidentified antibodies to the CD4bs exist in some HIV-1 sera, suggesting that new approaches to present this conserved region of gp120 to the immune system may result in vaccine immunogens that elicit broadly NAbs.
| Li, Yuxing; Svehla, Krisha; Louder, Mark K et al. (2009) Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals. J Virol 83:1045-59 |
| Dey, Barna; Pancera, Marie; Svehla, Krisha et al. (2007) Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. J Virol 81:5579-93 |
| Li, Yuxing; Migueles, Stephen A; Welcher, Brent et al. (2007) Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat Med 13:1032-4 |
| Li, Y; Svehla, K; Mathy, N L et al. (2006) Characterization of antibody responses elicited by human immunodeficiency virus type 1 primary isolate trimeric and monomeric envelope glycoproteins in selected adjuvants. J Virol 80:1414-26 |
