Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor Status
Antibodies (Abs) play a central role in human immunodeficiency virus (HIV) protection due to their multiple functional inhibitory activities. W614A-3S Abs recognize a specific form of a highly conserved motif of the gp41 envelope protein and can elicit viral neutralization to protect CD4+ T cells. H...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-08-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417302797 |
| _version_ | 1818670398141628416 |
|---|---|
| author | Olivier Lucar Bin Su Valérie Potard Assia Samri Brigitte Autran Christiane Moog Patrice Debré Vincent Vieillard |
| author_facet | Olivier Lucar Bin Su Valérie Potard Assia Samri Brigitte Autran Christiane Moog Patrice Debré Vincent Vieillard |
| author_sort | Olivier Lucar |
| collection | DOAJ |
| description | Antibodies (Abs) play a central role in human immunodeficiency virus (HIV) protection due to their multiple functional inhibitory activities. W614A-3S Abs recognize a specific form of a highly conserved motif of the gp41 envelope protein and can elicit viral neutralization to protect CD4+ T cells. Here, we describe in detail the neutralizing profile of W614A-3S Abs in untreated long-term non-progressor (LTNP) HIV-infected patients. W614A-3S Abs were detected in 23.5% (16/68) of untreated LTNP patients compared with <5% (5/104) of HIV-1 progressor patients. The W614A-3S Abs had efficient neutralizing activity that inhibited transmitted founder primary viruses and exhibited Fc-mediated inhibitory functions at low concentrations in primary monocyte-derived macrophages. The neutralizing capacity of W614A-3S Abs was inversely correlated with viral load (r = −0.9013; p < 0.0001), viral DNA (r = −0.7696; p = 0.0005) and was associated the preservation of high CD4+ T-cell counts and T-cell responses. This study demonstrates that W614A-3S neutralizing Abs may confer a crucial advantage to LTNP patients. These results provide insights for both pathophysiological research and the development of vaccine strategies. |
| first_indexed | 2024-12-17T07:07:28Z |
| format | Article |
| id | doaj.art-dd31f954b9dd444cbf678d85eb7d0e2d |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-17T07:07:28Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-dd31f954b9dd444cbf678d85eb7d0e2d2022-12-21T21:59:07ZengElsevierEBioMedicine2352-39642017-08-0122C12213210.1016/j.ebiom.2017.07.007Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor StatusOlivier Lucar0Bin Su1Valérie Potard2Assia Samri3Brigitte Autran4Christiane Moog5Patrice Debré6Vincent Vieillard7Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, FranceU1109 INSERM, FMTS, Université de Strasbourg, Strasbourg, FranceSorbonne Universités, UPMC Univ Paris 06, UMR-S 1136, Paris, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, FranceU1109 INSERM, FMTS, Université de Strasbourg, Strasbourg, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, FranceAntibodies (Abs) play a central role in human immunodeficiency virus (HIV) protection due to their multiple functional inhibitory activities. W614A-3S Abs recognize a specific form of a highly conserved motif of the gp41 envelope protein and can elicit viral neutralization to protect CD4+ T cells. Here, we describe in detail the neutralizing profile of W614A-3S Abs in untreated long-term non-progressor (LTNP) HIV-infected patients. W614A-3S Abs were detected in 23.5% (16/68) of untreated LTNP patients compared with <5% (5/104) of HIV-1 progressor patients. The W614A-3S Abs had efficient neutralizing activity that inhibited transmitted founder primary viruses and exhibited Fc-mediated inhibitory functions at low concentrations in primary monocyte-derived macrophages. The neutralizing capacity of W614A-3S Abs was inversely correlated with viral load (r = −0.9013; p < 0.0001), viral DNA (r = −0.7696; p = 0.0005) and was associated the preservation of high CD4+ T-cell counts and T-cell responses. This study demonstrates that W614A-3S neutralizing Abs may confer a crucial advantage to LTNP patients. These results provide insights for both pathophysiological research and the development of vaccine strategies.http://www.sciencedirect.com/science/article/pii/S2352396417302797HIV-1Long-term non-progressorsNeutralizing antibody |
| spellingShingle | Olivier Lucar Bin Su Valérie Potard Assia Samri Brigitte Autran Christiane Moog Patrice Debré Vincent Vieillard Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor Status EBioMedicine HIV-1 Long-term non-progressors Neutralizing antibody |
| title | Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor Status |
| title_full | Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor Status |
| title_fullStr | Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor Status |
| title_full_unstemmed | Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor Status |
| title_short | Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor Status |
| title_sort | neutralizing antibodies against a specific human immunodeficiency virus gp41 epitope are associated with long term non progressor status |
| topic | HIV-1 Long-term non-progressors Neutralizing antibody |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417302797 |
| work_keys_str_mv | AT olivierlucar neutralizingantibodiesagainstaspecifichumanimmunodeficiencyvirusgp41epitopeareassociatedwithlongtermnonprogressorstatus AT binsu neutralizingantibodiesagainstaspecifichumanimmunodeficiencyvirusgp41epitopeareassociatedwithlongtermnonprogressorstatus AT valeriepotard neutralizingantibodiesagainstaspecifichumanimmunodeficiencyvirusgp41epitopeareassociatedwithlongtermnonprogressorstatus AT assiasamri neutralizingantibodiesagainstaspecifichumanimmunodeficiencyvirusgp41epitopeareassociatedwithlongtermnonprogressorstatus AT brigitteautran neutralizingantibodiesagainstaspecifichumanimmunodeficiencyvirusgp41epitopeareassociatedwithlongtermnonprogressorstatus AT christianemoog neutralizingantibodiesagainstaspecifichumanimmunodeficiencyvirusgp41epitopeareassociatedwithlongtermnonprogressorstatus AT patricedebre neutralizingantibodiesagainstaspecifichumanimmunodeficiencyvirusgp41epitopeareassociatedwithlongtermnonprogressorstatus AT vincentvieillard neutralizingantibodiesagainstaspecifichumanimmunodeficiencyvirusgp41epitopeareassociatedwithlongtermnonprogressorstatus |