Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors.

Abstract

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.

• Authors: Nuria González, Krisha McKee, Rebecca M Lynch, Ivelin S Georgiev, Laura Jimenez, Eulalia Grau, Eloísa Yuste, Peter D Kwong, John R Mascola, José Alcamí
• Journal: PloS one (PLoS One) Vol. 13 Issue 3 Pg. e0193773 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 29558468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• CD4 Antigens
• HIV Antibodies
• Polysaccharides

Topics

• Antibodies, Neutralizing (blood)
• CD4 Antigens (blood)
• Cohort Studies
• Disease Progression
• Disease Resistance (immunology)
• Enzyme-Linked Immunosorbent Assay
• Epitope Mapping
• HEK293 Cells
• HIV Antibodies (blood)
• HIV Infections (immunology)
• HIV Long-Term Survivors
• HIV-1 (immunology)
• Humans
• Neutralization Tests
• Polysaccharides (immunology)
• Spain