MOLBA04 - Oral Abstract
Comparative activity of IgA mediated antibody dependent cell-mediated cytotoxicity (ADCC) in the genital mucosa of HIV seroconverters and highly exposed seronegative women
Presented by Linda Baum (United States).
M. Aziz1,2, M. Mata1, F. Mahmood1, H. Durkin3, C. Liu4, R. Greenblatt5, M. Nowicki6, E. Golub7, K. Anastos8, A. French1,2, L. Baum1
1Rush University Medical Center, Chicago, United States, 2Cook County Health & Hospital Systems, Chicago, United States, 3SUNY Downstate Medical Center, Brooklyn, United States, 4Georgetown University, Washington, United States, 5University of California, San Francisco, United States, 6University of Southern California Norris Hospital, Los Angeles, United States, 7Johns Hopkins University, Baltimore, United States, 8Montefiore Medical Center, Section of Infectious Diseases, Bronx, United States
Background: The potential role of
ADCC in prevention of infection is suggested by the RV144 HIV vaccine trial
where non-neutralizing antibodies contributed to protection against infection
with HIV. Studies from Kenya showed that
HIV specific IgA in cervical fluid was present in uninfected sex workers. We
aimed to analyze cervicovaginal lavage fluid(CVL) from 2 seroconverters (SC)
and 10 highly exposed seronegative women who had unprotected sex with known
Methods: A 51Cr-release
assay with natural killer cells or monocytes as effectors was used to measure
IgG or IgA mediated ADCC against clade specific gp120 coupled target cells. We
analyzed CVL from ESN at one visit, and SC at intervals from one yr
pre-seroconversion (PSC) to 6.5 yr after seroconversion (ASC). We evaluated
activity at 4, 10 fold serial dilutions starting with a 1/10 dilution.
Results: Figure 1 (top)shows shows minimal to no activity of IgG mediated ADCC in the CVL of 10 ESN.
Figure 1(bottom) shows IgA
mediated ADCC in the CVL of the same 10 ESN.
4 patients show significant activity above background activity. At the peak dilution, patient 4 shows 27.3% Specific
Release (SR) , patient 6 shows 14.5 %SR, patient 8 shows 17.9 %SR and patient 10 shows 17.6% SR.
Figures 2 and 3 shows no IgA mediated ADCC activity in CVL of 2
seroconverters from PSC to 6.5 years ASC even while IgG activity is present in
Conclusions: HIV IgA in CVL samples was associated with ADCC and lack
of HIV infection in exposed women, indicating that genital HIV IgA may
contribute to protection from infection. Further
studies need to be done to determine if IgA mediated ADCC antibodies may be
protective in ESN.
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