HIV-specific antibody-dependent cellular cytotoxicity: a novel vaccine modality

2012 ◽  
Vol 8 (8) ◽  
pp. 767-774 ◽  
Author(s):  
Vijaya Madhavi ◽  
Stephen J Kent ◽  
Ivan Stratov
Keyword(s):  
Specific Antibody ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity

scholarly journals Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/macEnvelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Benjamin von Bredow ◽  
Raiees Andrabi ◽  
Michael Grunst ◽  
Andres G. Grandea ◽  
Khoa Le ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Specific Antibody ◽  
Neutralizing Antibody ◽  
Glycosylation Site ◽  
Antibody Binding ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Broadly Neutralizing Antibody ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTAs a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/maclineage express phylogenetically and antigenically distinct envelope glycoproteins. Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIVsmm/macisolates. Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/macinfectivity. Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody. Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization. These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers. To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/macEnv and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCEHere we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity. This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/macEnv and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.

scholarly journals HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) -Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0145249 ◽  
Author(s):  
Sanne Skov Jensen ◽  
Anders Fomsgaard ◽  
Marie Borggren ◽  
Jeanette Linnea Tingstedt ◽  
Jan Gerstoft ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Specific Antibody ◽  
Cell Function ◽  
Nk Cell ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity

scholarly journals Critical role for monocytes in mediating HIV-specific antibody-dependent cellular cytotoxicity

Retrovirology ◽  
2012 ◽  
Vol 9 (S2) ◽  
Author(s):  
M Kramski ◽  
GF Lichtfuss ◽  
A Schorcht ◽  
AP Johnston ◽  
R De Rose ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Critical Role ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity

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

2017 ◽  
Vol 91 (18) ◽  
Author(s):  
Vijaya Madhavi ◽  
Bruce D. Wines ◽  
Janaki Amin ◽  
Sean Emery ◽  
Ester Lopez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Hiv Infection ◽  
Specific Antibody ◽  
Cell Activation ◽  
Nk Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Elite Controllers ◽  
Hiv Replication

ABSTRACT Studying HIV-infected individuals who control HIV replication (elite controllers [ECs]) enables exploration of effective anti-HIV immunity. HIV Env-specific and non-Env-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 FcγRIIIa (rsFcγRIIIa)-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 FcγRIIIa, activating NK cells, and mediating granzyme B activity (all P < 0.01) than viremic subjects. ECs also had higher levels of antibodies against a C-terminal 13-mer Vpu peptide capable of mediating FcγRIIIa binding and NK cell activation than viremic subjects (both P < 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.

scholarly journals Influence of Cytokines on HIV-Specific Antibody-Dependent Cellular Cytotoxicity Activation Profile of Natural Killer Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38580 ◽  
Author(s):  
Leia Wren ◽  
Matthew S. Parsons ◽  
Gamze Isitman ◽  
Robert J. Center ◽  
Anthony D. Kelleher ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Specific Antibody ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Killer Cells ◽  
Activation Profile
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