Breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity

Madhavi, Vijaya; Wren, Leia; Center, Rob J.; Gonelli, Christopher A.; Winnall, Wendy Rachael; Parsons, Matthew S.; Kramski, Marit; Kent, Stephen J.; Stratov, Ivan

doi:10.1097/qad.0000000000000310

Cited by 36 publications

(31 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2E). The higher levels of Env-specific dimeric rsFc␥RIIIa-binding antibodies at low serum dilutions (1:10) despite similar overall titers may suggest greater breadth of epitope coverage in the ECs, consistent with our previous ADCC studies in slow progressors (9,10). Alternatively, this improved EC plasma binding to the rsFc␥RIIIa could suggest that EC plasma either binds gp140 more effectively or binds the rsFc␥RIIIa more effectively.…”

Section: Resultssupporting

confidence: 70%

“…ADCC responses have also been shown to develop rapidly following infection with HIV-1, which suggests that these responses could contribute to HIV control at the early stages of infection (38,39). We previously showed a role for ADCC in HIV control in viremic controllers (9,10,40). However, data on the role for ADCC in ECs is limited.…”

Section: Discussionmentioning

confidence: 92%

“…In order to corroborate our finding using a dimeric rsFc␥RIIIa binding assay with a functional ADCC assay, we first performed antibody-mediated NK cell activation assays. This assay studies the ability of Env-or Vpu-specific antibodies to induce cytokine (gamma interferon [IFN-␥]) expression and/or degranulation (CD107a expression) in gated NK cells (9,26). We found that Env-specific antibodies in the sera of ECs induced a higher proportion of NK cells to express IFN-␥ and/or CD107a than those in FIG 3 EC antibodies dissociate from gp140 more slowly than antibodies from viremic subjects.…”

Section: Figmentioning

confidence: 91%

“…ECs are a model to study HIV control (9,18,19), and we recruited 22 ECs to provide serum samples and matched these subjects to 44 viremic subjects. The clinical characteristics of the subjects are shown in Tables 1 and 2.…”

Section: Resultsmentioning

confidence: 99%

“…Several viral, . There is increasing evidence from studies in both humans and macaques that correlate robust ADCC responses with slow disease progression (9,10,36,37). ADCC responses have also been shown to develop rapidly following infection with HIV-1, which suggests that these responses could contribute to HIV control at the early stages of infection (38,39).…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV

Madhavi

Wines

Amin

et al. 2017

J Virol

Self Cite

View full text Add to dashboard Cite

Studying HIV-infected individuals who control HIV replication (elite controllers [ECs]) enables exploration of effective anti-HIV immunity. HIV Env-specific and nonEnv-specific antibody-dependent cellular cytotoxicity (ADCC) may contribute to protection from progressive HIV infection, but the evidence is limited. We recruited 22 ECs and matched them with 44 viremic subjects. HIV Env-and Vpu-specific ADCC responses in sera were studied using a novel enzyme-linked immunosorbent assay (ELISA)-based dimeric recombinant soluble Fc␥RIIIa (rsFc␥RIIIa)-binding assay, surface plasmon resonance, antibody-dependent natural killer (NK) cell activation assays, and ADCC-mediated killing assays. ECs had higher levels of HIV Env-specific antibodies capable of binding Fc␥RIIIa, activating NK cells, and mediating granzyme B activity (all P Ͻ 0.01) than viremic subjects. ECs also had higher levels of antibodies against a C-terminal 13-mer Vpu peptide capable of mediating Fc␥RIIIa binding and NK cell activation than viremic subjects (both P Ͻ 0.05). Our data associate Env-specific and Vpu epitope-specific ADCC in effective immune responses against HIV among ECs. Our findings have implications for understanding the role of ADCC in HIV control.IMPORTANCE Understanding immune responses associated with elite control of HIV may aid the development of immunotherapeutic and vaccine strategies for controlling HIV infection. Env is a major HIV protein target of functional antibody responses that are heightened in ECs. Interestingly, EC antibodies also target Vpu, an accessory protein crucial to HIV, which degrades CD4 and antagonizes tetherin. Antibodies specific to Vpu are a common feature of the immune response of ECs that may prove to be of functional importance to the design of improved ADCC-based immunotherapy and preventative HIV vaccines.

show abstract

Section: Resultssupporting

confidence: 70%

Section: Discussionmentioning

confidence: 92%

Section: Figmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV

Madhavi

Wines

Amin

et al. 2017

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

Mining HIV controllers for broad and functional antibodies to recognize and eliminate HIV-infected cells

et al. 2021

View full text Add to dashboard Cite

show abstract

HIV-specific CD4-induced Antibodies Mediate Broad and Potent Antibody-dependent Cellular Cytotoxicity Activity and are Commonly Detected in Plasma from HIV-infected Humans

et al. 2015

View full text Add to dashboard Cite

HIV-specific antibodies (Abs) can reduce viral burden by blocking new rounds of infection or by destroying infected cells via activation of effector cells through Fc–FcR interaction. This latter process, referred to as antibody-dependent cellular cytotoxicity (ADCC), has been associated with viral control and improved clinical outcome following both HIV and SIV infections. Here we describe an HIV viral-like particle (VLP)-based sorting strategy that led to identification of HIV-specific memory B cells encoding Abs that mediate ADCC from a subtype A-infected Kenyan woman at 914 days post-infection. Using this strategy, 12 HIV-envelope-specific monoclonal antibodies (mAbs) were isolated and three mediated potent ADCC activity when compared to well-characterized ADCC mAbs. The ADCC-mediating Abs also mediated antibody-dependent cell-mediated virus inhibition (ADCVI), which provides a net measure of Fc receptor-triggered effects against replicating virus. Two of the three ADCC-mediating Abs targeted a CD4-induced (CD4i) epitope also bound by the mAb C11; the third antibody targeted the N-terminus of V3. Both CD4i Abs identified here demonstrated strong cross-clade breadth with activity against 10 of 11 envelopes tested, including those from clades A, B, C, A/D and C/D, whereas the V3-specific antibody showed more limited breadth. Variants of these CD4i, C11-like mAbs engineered to interrupt binding to FcγRs inhibited a measurable percentage of the donor's ADCC activity starting as early as 189 days post-infection. C11-like antibodies also accounted for between 18–78% of ADCC activity in 9 chronically infected individuals from the same cohort study. Further, the two CD4i Abs originated from unique B cells, suggesting that antibodies targeting this epitope can be commonly produced. Taken together, these data provide strong evidence that CD4i, C11-like antibodies develop within the first 6 months of infection and they can arise from unique B-cell lineages in the same individual. Further, these mAbs mediate potent plasma IgG-specific ADCC breadth and potency and contribute to ADCC activity in other HIV-infected individuals.

show abstract

Breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity

Abstract: HIV controllers have robust ADCC responses that recognize a broad range of HIV-1 Env. Glycosylation of Env was found to be important for recognition of ADCC epitopes. Identifying conserved ADCC epitopes will assist in designing globally relevant ADCC-based HIV vaccines.

Cited by 36 publications

References 52 publications

HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV

HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV

Mining HIV controllers for broad and functional antibodies to recognize and eliminate HIV-infected cells

HIV-specific CD4-induced Antibodies Mediate Broad and Potent Antibody-dependent Cellular Cytotoxicity Activity and are Commonly Detected in Plasma from HIV-infected Humans

Contact Info

Product

Resources

About