title: The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells.
abstract: Despite the risk of transmitting HIV-1, mothers in resource-poor areas are encouraged to breastfeed their infants because of beneficial immunologic and nutritional factors in milk. Interestingly, in the absence of antiretroviral prophylaxis, the overwhelming majority of HIV-1-exposed, breastfeeding infants are naturally protected from infection. To understand the role of HIV-1 envelope (Env)-specific antibodies in breast milk in natural protection against infant virus transmission, we produced 19 HIV-1 Env-specific monoclonal antibodies (mAbs) isolated from colostrum B cells of HIV-1-infected mothers and investigated their specificity, evolution, and anti-HIV-1 functions. Despite the previously reported genetic compartmentalization and gp120-specific bias of colostrum HIV Env-specific B cells, the colostrum Env-specific mAbs described here demonstrated a broad range of gp120 epitope specificities and functions, including inhibition of epithelial cell binding and dendritic cell-mediated virus transfer, neutralization, and antibody-dependent cellular cytotoxicity. We also identified divergent patterns of colostrum Env-specific B-cell lineage evolution with respect to crossreactivity to gastrointestinal commensal bacteria, indicating that commensal bacterial antigens play a role in shaping the local breast milk immunoglobulin G (IgG) repertoire. Maternal vaccine strategies to specifically target this breast milk B-cell population may be necessary to achieve safe breastfeeding for all HIV-1-exposed infants.
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Jeffries
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Sacha
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pollara
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: J
authors.initials: J
authors.lastname: Himes
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: F H
authors.initials: FH
authors.lastname: Jaeger
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Dennison
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: E
authors.initials: E
authors.lastname: McGuire
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kunz
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Eudailey
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Trama
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: C
authors.initials: C
authors.lastname: LaBranche
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Fouda
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: K
authors.initials: K
authors.lastname: Wiehe
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: H-X
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Department of Surgery, Duke University, Durham, North Carolina, USA.
authors.forename: G
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Permar
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D000915:Antibody Affinity; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D001942:Breast Feeding; D003126:Colostrum / Q000166:cytology / Q000276:immunology* / Q000821:virology; D003429:Cross Reactions; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D060467:Disease Resistance / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008895:Milk, Human / Q000737:chemistry / Q000276:immunology / Q000821:virology; D011247:Pregnancy; D013559:Symbiosis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G