Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

Kristensen, Anne B.; Lay, William N.; Ana-Sosa-Batiz, Fernanda; Vanderven, Hillary A.; Madhavi, Vijaya; Laurie, Karen; Carolan, Louise; Wines, Bruce D.; Hogarth, P. Mark; Wheatley, Adam K.; Kent, Stephen J.

doi:10.1128/jvi.00285-16

Cited by 53 publications

(61 citation statements)

References 42 publications

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“…To quantitate antibodies capable of binding Fc␥R, we recently developed a highthroughput enzyme-linked immunosorbent assay (ELISA)-based assay to measure the ability of influenza virus-specific ADCC antibodies to bind dimeric recombinant soluble Fc␥RIIIa (rsFc␥RIIIa) ectodomains (22)(23)(24). We adapted this assay to study the ability of HIV-specific antibodies to bind higher-affinity dimeric rsFc␥RIIIa ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The dimeric rsFc␥RIIIa ELISA-based assay to measure the binding of HIV-specific antibodies to Fc␥RIIIa is a relatively novel approach to studying functional antibodies for HIV, having previously been used to study influenza virus-specific antibodies (22)(23)(24). Commonly used ADCC assays can be difficult to reproduce across laboratories due to variability of effector and target cells, and they are difficult to perform on a large scale.…”

Section: Discussionmentioning

confidence: 99%

“…HIV antibody binding to Fc␥ receptors was measured in vitro using a dimeric recombinant soluble Fc␥RIIIa (rsFc␥RIIIa)-binding assay recently described as a sensitive measure of influenza virus-specific ADCC antibodies (22)(23)(24). This novel assay uses dimeric rsFc␥RIIIa proteins to evaluate the cross-linking of pairs of antibody Fc by Fc␥Rs, thereby modeling their potential to activate effector cells.…”

Section: Methodsmentioning

confidence: 99%

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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

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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

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“…A rsFcγR dimer ELISA was employed to model the need for ADCC-inducing Abs to cross-link FcγRs as previously described (31,35). This assay demonstrated a stronger correlation with Ab-dependent NK cell activation than a standard IgG ELISA (31).…”

Section: Methodsmentioning

confidence: 99%

“…The reaction was stopped with 1 M HCl and absorbance read at 450 nm. Intragam 5 (5 μg/ml, bioCSL) was used as a positive control and allowed for normalization between plates as previously described (31,35).…”

Section: Methodsmentioning

confidence: 99%

Fc functional antibodies in humans with severe H7N9 and seasonal influenza

Vanderven¹,

Liu²,

Ana-Sosa-Batiz³

et al. 2017

JCI Insight

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Bidirectionally Regulating Viral and Cellular Ferroptosis with Metastable Iron Sulfide Against Influenza Virus

et al. 2023

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Influenza virus with numerous subtypes and frequent variation limits the development of high-efficacy and broad-spectrum antiviral strategy. Here, a novel multi-antiviral metastable iron sulfides (mFeS) against various influenza A/B subtype viruses is developed. This work finds that mFeS induces high levels of lipid peroxidation and •OH free radicals in the conservative viral envelope, which depends on Fe 2+ . This phenomenon, termed as a viral ferroptosis, results in the loss of viral infectibility and pathogenicity in vitro and in vivo, respectively. Furthermore, the decoction of mFeS (Dc(mFeS)) inhibits cellular ferroptosis-dependent intracellular viral replication by correcting the virus-induced reprogrammed sulfur metabolism, a conserved cellular metabolism. Notably, personal protective equipment (PPE) that is loaded with mFeS provides good antiviral protection. Aerosol administration of mFeS combined with the decoction (mFeS&Dc) has a potential therapeutic effect against H1N1 lethal infection in mice. Collectively, mFeS represents an antiviral alternative with broad-spectrum activity against intracellular and extracellular influenza virus.

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Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

Cited by 53 publications

References 42 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

Fc functional antibodies in humans with severe H7N9 and seasonal influenza

Bidirectionally Regulating Viral and Cellular Ferroptosis with Metastable Iron Sulfide Against Influenza Virus

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