| Title: |
V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1 |
| Authors: |
Morgand, Marion; Bouvin-Pley, Mélanie; Plantier, Jean-Christophe; Alain, Moreau; Alessandri, Elodie; Simon, François; Pace, Craig S.; Pancera, Marie; Ho, David D.; Poignard, Pascal; Bjorkman, Pamela J.; Mouquet, Hugo; Nussenzweig, Michel C.; Kwong, Peter D.; Baty, Daniel; Chames, Patrick; Braibant, Martine; Barin, Francis |
| Contributors: |
Morphogénèse et antigénicité du VIH, des Virus des Hépatites et Emergents (MAVIVHe); Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); CHU Rouen; Normandie Université (NU); Laboratoire de Virologie CHU Saint-Louis; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Aaron Diamond AIDS Research Center New York; Rockefeller University New York; Vaccine Research Center Betesda; National Institutes of Health Bethesda, MD, USA (NIH); Department of Immunology and Microbial Sciences La Jolla; The Scripps Research Institute La Jolla, San Diego; California Institute of Technology (CALTECH); Réponse humorale aux pathogènes; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM); Howard Hughes Medical Institute New York; Centre de Recherche en Cancérologie de Marseille (CRCM); Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
ISSN: 1525-4135. |
| Publisher Information: |
CCSD; Lippincott, Williams & Wilkins |
| Publication Year: |
2016 |
| Collection: |
Université François-Rabelais de Tours: HAL |
| Subject Terms: |
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Structural Biology [q-bio.BM] |
| Description: |
International audience ; Background: Highly potent broadly neutralizing monoclonal antibodies (bNAbs) have been obtained from individuals infected by HIV-1 group M variants. We analyzed the cross-group neutralization potency of these bNAbs toward non-M primary isolates (PI).Material and Methods: The sensitivity to neutralization was analyzed in a neutralization assay using TZM-bl cells. Twenty-three bNAbs were used, including reagents targeting the CD4-binding site, the N160 glycan-V1/V2 site, the N332 glycan-V3 site, the membrane proximal external region of gp41, and complex epitopes spanning both env subunits. Two bispecific antibodies that combine the inhibitory activity of an anti-CD4 with that of PG9 or PG16 bNAbs were included in the study (PG9-iMab and PG16-iMab).Results: Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O PIs, 1 group N PI, and the group P PI were neutralized by PG9 and/or PG16 or PGT145 at low concentrations (0.04–9.39 µg/mL). None of the non-M PIs was neutralized by the bNAbs targeting other regions at the highest concentration tested, except 10E8 that neutralized weakly 2 group N PIs and 35O22 that neutralized 1 group O PI. The bispecific bNAbs neutralized very efficiently all the non-M PIs with IC50 below 1 µg/mL, except 2 group O strains.Conclusion: The N160 glycan-V1/V2 site is the most conserved neutralizing site within the 4 groups of HIV-1. This makes it an interesting target for the development of HIV vaccine immunogens. The corresponding bNAbs may be useful for immunotherapeutic strategies in patients infected by non-M variants. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/26413851; PUBMED: 26413851; PUBMEDCENTRAL: PMC4770367 |
| DOI: |
10.1097/QAI.0000000000000854 |
| Availability: |
https://hal.univ-grenoble-alpes.fr/hal-01314296; https://hal.univ-grenoble-alpes.fr/hal-01314296v1/document; https://hal.univ-grenoble-alpes.fr/hal-01314296v1/file/qai-71-237.pdf; https://doi.org/10.1097/QAI.0000000000000854 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.274E40B2 |
| Database: |
BASE |