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Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies
- Publication Year :
- 2017
- Publisher :
- The University of North Carolina at Chapel Hill University Libraries, 2017.
-
Abstract
- A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.
- Subjects :
- Male
0301 basic medicine
Cytidine deaminase activity
Lineage (genetic)
Somatic hypermutation
Crystallography, X-Ray
Article
Epitope
Virus
Affinity maturation
03 medical and health sciences
Neutralization Tests
Polysaccharides
Humans
Neutralizing antibody
Phylogeny
biology
env Gene Products, Human Immunodeficiency Virus
General Medicine
Antibodies, Neutralizing
Virology
030104 developmental biology
Mutation
HIV-1
biology.protein
Antibody
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....21e4004ab2fbc9d660aa20bf8b617bd5
- Full Text :
- https://doi.org/10.17615/a0m6-td59