title: HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant.
abstract: HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at ∼1 year post-infection, including one with cross-clade breadth. The nAbs bind to envelope trimer from the transmitted virus, suggesting that this interaction may have initiated development of the infant nAbs. The infant cross-clade bnAb targets the N332 supersite on envelope but, unlike adult bnAbs targeting this site, lacks indels and has low SHM. The identification of this infant bnAb illustrates that HIV-1-specific neutralization breadth can develop without prolonged affinity maturation and extensive SHM.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Medical Scientist Training Program, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Cassandra A
authors.initials: CA
authors.lastname: Simonich
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Williams
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Hans P
authors.initials: HP
authors.lastname: Verkerke
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Williams
authors.affiliation: Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nduati
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Lee
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Medical Scientist Training Program, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: joverbau@fredhutch.org.
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000235:genetics* / Q000276:immunology; D000939:Epitopes; D015483:HIV Antibodies / Q000097:blood / Q000235:genetics* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120