Reconstruction of a polyclonal ADCC antibody repertoire from an HIV-1 non-transmitting mother
Zak A. Yaffe,
Shilei Ding,
Kevin Sung,
Vrasha Chohan,
Lorie Marchitto,
Laura Doepker,
Duncan Ralph,
Ruth Nduati,
Frederick A. Matsen, IV,
Andrés Finzi,
Julie Overbaugh
Affiliations
Zak A. Yaffe
Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA; Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA
Shilei Ding
Centre de Recherche du CHUM (CRCHUM), Montréal, QC H2X 0A9, Canada
Kevin Sung
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Vrasha Chohan
Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Lorie Marchitto
Centre de Recherche du CHUM (CRCHUM), Montréal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada
Laura Doepker
Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Duncan Ralph
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
Ruth Nduati
Department of Paediatrics and Child Health, University of Nairobi, Kenyatta National Hospital, Nairobi, Kenya
Frederick A. Matsen, IV
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA
Andrés Finzi
Centre de Recherche du CHUM (CRCHUM), Montréal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada
Julie Overbaugh
Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Corresponding author
Summary: Human natural history and vaccine studies support a protective role of antibody dependent cellular cytotoxicity (ADCC) activity against many infectious diseases. One setting where this has consistently been observed is in HIV-1 vertical transmission, where passively acquired ADCC activity in HIV-exposed infants has correlated with reduced acquisition risk and reduced pathogenesis in HIV+ infants. However, the characteristics of HIV-specific antibodies comprising a maternal plasma ADCC response are not well understood. Here, we reconstructed monoclonal antibodies (mAbs) from memory B cells from late pregnancy in mother MG540, who did not transmit HIV to her infant despite several high-risk factors. Twenty mAbs representing 14 clonal families were reconstructed, which mediated ADCC and recognized multiple HIV Envelope epitopes. In experiments using Fc-defective variants, only combinations of several mAbs accounted for the majority of plasma ADCC of MG540 and her infant. We present these mAbs as evidence of a polyclonal repertoire with potent HIV-directed ADCC activity.
