Preexposure passive transfer predicts plasma antibody levels prevent HIV-I aquisition

Abstract

Background: It is widely appreciated that effective human vaccines directed against viral pathogens elicit neutralizing antibodies (NAbs). During the past four years, a new generation of potent broadly reacting neutralizing monoclonal antibodies (mAbs) have been isolated from HIV-I infected individuals. These mAbs typically exhibit great breadth and potency against heterologous HIV isolates when assayed for neutralization in vitro. The passive transfer of anti-HIV l neutralizing antibodies conferring sterilizing immunity to macaques has been used to determine the plasma neutralization titers, which must be present at the time of exposure to prevent acquisition of SIV/HIV chimeric virus (SHIV) infections. Methods: In this study, five recently isolated potent and broadly acting anti-HIV neutralizing mAbs, interacting with the HIV l gp 120 CD4 binding site (VRCO I, 45-46 m^2 and 3BNC 117) or dependent on the gp120 N332 glycan, (10-1074 and PGTl2l) were individually administered to 60 rhesus monkeys, which were challenged intrarectally 24 hours later with either of two different R5-tropic SHIVs. Results: Of the 5 neutralizing mAbs evaluated, PGT121 was clearly the most effective against both viruses. In addition to measuring the plasma concentrations of the different mAbs at the time of challenge and their respective in vivo half lives, the corresponding protective neutralization titers were also determined. By combining the results obtained from 60 challenged animals, we determined that the protective neutralization titer in plasma preventing virus acquisition in 50% of the exposed monkeys was approximately 1:100. Conclusion: These results are informative for establishing a threshold level of protective neutralizing activity to be induced by a prophylactic HIV I vaccine.

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