Abstract

BackgroundWe measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed women during HIV seroconversion.MethodsPlasma and cervico-vaginal lavage (CVL) fluid from 11 seroconverters (SC) were analyzed biannually from one year pre- to 6 year post-seroconversion using a 51Cr-release assay to measure HIV-1 gp120 specific ADCC.ResultsNo SC had significant HIV specific CVL ADCC activity before seroconversion or until 1.5 yr after seroconversion. One individual had a %Specific Release (SR) of 25.4 at 2 years, 26.7 at 3 years and 21.0 at 4 years after seroconversion in CVL. Another sample had 4.7% SR at 2 years, 5.3 at 3 years, 10.9 at 4 years, and 8.4 at 5 years after seroconversion in CVL. A third had no activity until 17% SR 5 years after seroconversion in CVL. A fourth showed activity of 36.5% SR at 6.5 years after seroconversion. Seven women had no ADCC activity in their CVL. Paired serum samples showed HIV specific ADCC activity prior to the appearance of CVL ADCC activity.ConclusionsHIV specific ADCC activity in CVL rose 2 years after seroconversion; ADCC was present in the serum prior to this time. These data suggest that genital tract ADCC activity is not present until well after acute infection.

Highlights

  • We measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed women during HIV seroconversion

  • HIV specific ADCC activity in cervico-vaginal lavage (CVL) rose 2 years after seroconversion; ADCC was present in the serum prior to this time

  • These data suggest that genital tract ADCC activity is not present until well after acute infection

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Summary

Introduction

We measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed women during HIV seroconversion. Further analysis of the results indicated that non-neutralizing antibodies, including antibodies that mediate ADCC against HIV, contributed significantly to the protection that was observed [2,3,4,5,6]. Studies subsequent to this trial support the protective effect of ADCC antibodies against retroviruses [7,8,9]. The most convincing of these recent studies shows that vaccination of rhesus macaques with a live attenuated SIV protects against vaginal challenge with a neutralization-resistant SIV strain which correlates with the presence of ADCC antibodies [10]. ADCC antibodies in breast milk are associated with reduced risk of mother-to-child transmission [11] and ADCC antibodies exert pressure that leads to generation of viral escape mutants [12]

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