Abstract

MOLBA04 - Oral Abstract Session

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. Aziz^1,2, M. Mata¹, F. Mahmood¹, H. Durkin³, C. Liu⁴, R. Greenblatt⁵, M. Nowicki⁶, E. Golub⁷, K. Anastos⁸, A. French^1,2, L. Baum<sup>1

1</sup>Rush 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 positive partners.
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.


[Figure 1]

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 later visits.


[Figure 2]




[Figure 3]


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.