HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV.
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.
HIV + AIDS
Partial efficacy of a broadly neutralizing antibody against cell-associated SHIV infection
Parsons MS, Lloyd SB, Lee WS, Kristensen AB, Amarasena T, Center RJ, Keele BF, Lifson JD, LaBranche CC, Montefiori D, Wines BD, Hogarth PM, Swiderek KM, Venturi V, Davenport MP, Kent SJ
HIV + AIDS
The core domain of hepatitis C virus glycoprotein E2 generates potent cross-neutralizing antibodies in guinea pigs.
Vietheer PT, Boo I, Gu J, McCaffrey K, Edwards S, Owczarek C, Hardy MP, Fabri L, Center RJ, Poumbourios P, Drummer HE
Differentiating founder and chronic HIV envelope sequences.
Murray JM, Maher S, Mota T, Suzuki K, Kelleher AD, Center RJ, Purcell D
Trimeric gp120-specific bovine monoclonal antibodies require cysteine and aromatic residues in CDRH3 for high affinity binding to HIV Env.
Heydarchi B, Center RJ, Bebbington J, Cuthbertson J, Gonelli C, Khoury G, Mackenzie C, Lichtfuss M, Rawlin G, Muller B, Purcell D