Neutralization profiles of newly transmitted human immunodeficiency virus type 1 by monoclonal antibodies 2G12, 2F5, and 4E10

Abstract

As the AIDS epidemic continues unabated, the development of a human immunodeficiency virus (HIV) vaccine is critical. Ideally, an effective vaccine should elicit cell-mediated and neutralizing humoral immune responses. We have determined the in vitro susceptibility profile of sexually transmitted viruses from 91 patients with acute and early HIV-1 infection to three monoclonal antibodies, 2G12, 2F5, and 4E10. Using a recombinant virus assay to measure neutralization, we found all transmitted viruses were neutralized by 4E10, 80% were neutralized by 2F5, and only 37% were neutralized by 2G12. We propose that the induction of 4E10-like antibodies should be a priority in designing immunogens to prevent HIV-1 infection.

FIG. 1.

Neutralization profile of each of the three MAbs. The mean IC₅₀ of the three MAbs (micrograms per milliliter), grouped on the x axis, is represented against the number of susceptible viral isolates on the y axis.

FIG. 2.

Recombinant viral assay to determine the sensitivity of patient-derived virus to the MAbs 2F5, 2G12, and 4E10. (A) Patient sample demonstrating susceptibility to all three MAbs: 2F5 (IC₅₀, 1.74 μg/ml), 2G12 (IC₅₀, 4.32 μg/ml), and 4E10 (IC₅₀, 1.88 μg/ml). (B) Patient sample susceptible to both 2F5 (IC₅₀, 6.49 μg/ml) and 4E10 (IC₅₀, 5.88 μg/ml) but not to 2G12 (IC₅₀, >50 μg/ml). (C) Susceptibility to 4E10 is preserved (IC₅₀, 8.87 μg/ml) in the face of resistance to both 2G12 (IC₅₀, >50 μg/ml) and 2F5 (IC₅₀, >50 μg/ml).