Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women

Abstract

Recent studies suggest that HIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies contribute to protective immunity against HIV. An important characteristic of future HIV vaccines will, therefore, be the ability to stimulate production of these antibodies in both men and women. Early studies suggest that men may have a better ADCC antibody response against HIV than women. Our objective was to determine whether men and women differ with respect to their ADCC response to HIV-1 gp120. HIV-positive, asymptomatic untreated men and women were matched for race, age, CD4+ T cell number, HIV-1 viral load, and treatment and HIV-1 gp120 ADCC antibody titers were compared. A standard 51 Cr-release assay was used to determine HIV-1 gp120 ADCC antibody titers in HIV-1-seropositive individuals from the Multicenter AIDS Cohort Study (MACS; n = 32) and the Women's Interagency HIV Study (WIHS; n = 32). Both sexes had high ADCC titers against HIV-1 gp120: 34.4% (n = 11) and 40.6% (n = 13) of men and women, respectively, had titers of 10,000; 62.5% (n = 20) and 56.3% (n = 18) had titers of 100,000. Groups did not differ in percent specific release (% SR), lytic units (LU), correlations of titer to viral load, or titer to CD4 + T cells in men or women. Both groups also had similar cross-clade ADCC antibody responses ( p > 0.5 for % SR and LU). Comparable groups of asymptomatic HIV-1-infected men and women had comparable HIV-1 gp120 ADCC antibodies. Both sexes had significant cross-clade reactivity. Differences between men and women may become evident as disease progresses; this should be evaluated at later stages of HIV-1 infection.

Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1–Infected Individuals from Guinea-Bissau and Denmark

“…Rather, the antibody specificity may differ perhaps by exposure of crossreactive neutralizing antibody epitopes or ADCC antibody epitopes. The neutralizing and ADCC activities of the two groups could not be correlated with gender (data not shown), which is in agreement with Mata et al 52 The Guinea-Bissau-specific subtypes A3, CRF02_AG, and A3/02 have previously been demonstrated to differ in disease progression, 26 but this did not reflect any variations in neutralization or ADCC activity in our assays (data not shown).…”

“…12,61 We found ADCC activity against both subtypes B and A Env in nearly all plasma samples, which is consistent with previous reports of crossclade ADCC activity in HIV-infected individuals. 46,52,61 The Guinea-Bissau plasma samples had increased ADCC activity against the subtype A Env, and we denote this as intraclade activity, as the subtypes A3, CRF02_AG, and A3/02 contain mainly the subtype A sequence in the env region. 62 Augmented intraclade-specific ADCC activity has been previously noted for the subtype B plasma, 46,52 but surprisingly in our study, the subtype B Danish samples did not show any enhanced ADCC activity against the subtype B Env.…”

“…46,52,61 The Guinea-Bissau plasma samples had increased ADCC activity against the subtype A Env, and we denote this as intraclade activity, as the subtypes A3, CRF02_AG, and A3/02 contain mainly the subtype A sequence in the env region. 62 Augmented intraclade-specific ADCC activity has been previously noted for the subtype B plasma, 46,52 but surprisingly in our study, the subtype B Danish samples did not show any enhanced ADCC activity against the subtype B Env. The higher ADCC activity in samples from Guinea-Bissau was not due to the concentrations of the primary IgG1 and IgG3 ADCCmediating antibodies 47 because a similar IgG antibody subclass distribution was observed in both groups.…”

Effects of cryopreservation on effector cells for antibody dependent cell-mediated cytotoxicity (ADCC) and natural killer (NK) cell activity in 51Cr-release and CD107a assays

“…NK cells respond immediately to virus infected cells and tumor cells; ADCC also requires participation of virus or tumor specific antibodies (Baum et al, 1996; Alpert et al, 2012; Kute et al, 2012; Yoshida et al, 2012; Mata et al, 2013). Both NK and ADCC activity are critical to defense against pathogens.…”

Development of IgG Mediated Antibody Dependent Cell-mediated Cytotoxicity (ADCC) in the Serum and Genital Mucosa of HIV Seroconverters

“…Since our assay measures ADCC activity against HIV-1 MNgp120, which is CXCR4 tropic, it is possible that these individuals did have ADCC against gp120 from a CCR5 tropic virus or against HIV peptides other than gp120. Evidence that suggests this is not likely to be the case includes: (1) studies that show that much of the ADCC against HIV is against HIV gp120 [ 42 ] and (2) studies in our lab and others which indicate that there is a great deal of cross reactivity in ADCC against different clades of HIV gp120 [ 43 , 44 ].…”