Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6879
Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors
Gonzalez-Fernandez, Nuria ISCIII | McKee, Krisha | Lynch, Rebecca M | Georgiev, Ivelin S | Jimenez, Laura | Grau, Eulalia | Yuste-Herranz, Maria Eloisa ISCIII | Kwong, Peter D | Mascola, John R | Alcamí, José ISCIII
PLoS One. 2018 Mar 20;13(3):e0193773.
BACKGROUND: Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. METHODS: Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses. bNAb specificities were studied by ELISA using mutated gp120, neutralization assays with mutated viruses, and peptide competition. Epitope specificities were also elucidated from the serum pattern of neutralization against a panel of diverse HIV-1 isolates. RESULTS: Broadly neutralizing sera were found among 9.3% LTNPs, both elite (7%) and viremic controllers (14%). Within the broadly neutralizing sera, CD4 binding site antibodies were detected by ELISA in 4/12 LTNPs (33%), and 16/33 of TPs (48%). Anti-MPER antibodies were detected in 6/12 LTNPs (50%) and 14/33 TPs (42%) whereas glycan-dependent HIV-1 bNAbs were more frequent in LTNPs (11/12, 92%) as compared to TPs (12/33, 36%). A good concordance between standard serum mapping and neutralization-based mapping was observed. CONCLUSION: LTNPs, both viremic and elite controllers, showed broad humoral immune responses against HIV-1, including activity against many major epitopes involved in bNAbs-mediated protection.
Antibodies, Neutralizing | CD4 Antigens | Cohort Studies | Disease Progression | Disease Resistance | Enzyme-Linked Immunosorbent Assay | Epitope Mapping | HEK293 Cells | HIV Antibodies | HIV Infections | HIV-1 | Humans | Neutralization Tests | Polysaccharides | Spain | HIV Long-Term Survivors
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