Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.

dc.contributor.author

Wiehe, Kevin

dc.contributor.author

Bradley, Todd

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Meyerhoff, R Ryan

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Hart, Connor

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Williams, Wilton B

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Easterhoff, David

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Faison, William J

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Kepler, Thomas B

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Saunders, Kevin O

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Alam, S Munir

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Bonsignori, Mattia

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Haynes, Barton F

dc.date.accessioned

2018-08-01T17:48:30Z

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2018-08-01T17:48:30Z

dc.date.issued

2018-06

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2018-08-01T17:48:26Z

dc.description.abstract

HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. One bottleneck for induction of bnAbs is the evolution of viral envelopes (Envs) that can select bnAb B cell receptors (BCR) with improbable mutations. Here we define the probability of bnAb mutations and demonstrate the functional significance of key improbable mutations in three bnAb B cell lineages. We show that bnAbs are enriched for improbable mutations, which implies that their elicitation will be critical for successful vaccine induction of potent bnAb B cell lineages. We discuss a mutation-guided vaccine strategy for identification of Envs that can select B cells with BCRs that have key improbable mutations required for bnAb development.

dc.identifier

S1931-3128(18)30219-1

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1931-3128

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1934-6069

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https://hdl.handle.net/10161/17301

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eng

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Elsevier BV

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Cell host & microbe

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10.1016/j.chom.2018.04.018

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Science & Technology

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Life Sciences & Biomedicine

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Microbiology

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Parasitology

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Virology

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SOMATIC HYPERMUTATION

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AFFINITY MATURATION

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GERMINAL-CENTERS

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VACCINE DESIGN

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STANDARDIZED ASSESSMENTS

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ENVELOPE PROTEIN

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ENV CLONES

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B-CELLS

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GERMLINE

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DISTINCT

dc.title

Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.

dc.type

Journal article

duke.contributor.orcid

Meyerhoff, R Ryan|0000-0003-1253-2250

duke.contributor.orcid

Williams, Wilton B|0000-0002-2970-7259

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Saunders, Kevin O|0000-0001-7399-7954

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Alam, S Munir|0000-0003-0941-0703

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Bonsignori, Mattia|0000-0003-2973-2101

pubs.begin-page

759

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765.e6

pubs.issue

6

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School of Medicine

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Duke

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Duke Human Vaccine Institute

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Institutes and Centers

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Medicine, Duke Human Vaccine Institute

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Medicine

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Clinical Science Departments

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Duke Cancer Institute

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Immunology

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Basic Science Departments

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Duke Global Health Institute

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University Institutes and Centers

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Institutes and Provost's Academic Units

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Surgery, Surgical Sciences

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Surgery

pubs.publication-status

Published

pubs.volume

23

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