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Title | HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage. |
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Journal, issue, pages | Immunity, Vol. 47, Issue 5, Page 990-1003.e9, Year 2017 |
Publish date | Nov 21, 2017 |
Authors | Elise Landais / Ben Murrell / Bryan Briney / Sasha Murrell / Kimmo Rantalainen / Zachary T Berndsen / Alejandra Ramos / Lalinda Wickramasinghe / Melissa Laird Smith / Kemal Eren / Natalia de Val / Mengyu Wu / Audrey Cappelletti / Jeffrey Umotoy / Yolanda Lie / Terri Wrin / Paul Algate / Po-Ying Chan-Hui / Etienne Karita / / / Andrew B Ward / Ian A Wilson / Dennis R Burton / Davey Smith / Sergei L Kosakovsky Pond / Pascal Poignard / |
PubMed Abstract | Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb ...Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design. |
External links | Immunity / PubMed:29166592 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 3.1 - 27.0 Å |
Structure data | EMDB-7089: EMDB-7104: EMDB-7105: EMDB-7106: EMDB-7107: EMDB-7108: PDB-5feh: |
Chemicals | ChemComp-SO4: ChemComp-EDO: ChemComp-HOH: |
Source |
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Keywords | IMMUNE SYSTEM / HIV / broadly neutralizing antibody / V1/V2 |