Reconstruction of a polyclonal ADCC antibody repertoire from an HIV-1 non-transmitting mother
Date
2023Author
Yaffe, Zak A
Ding, Shilei
Sung, Kevin
Chohan, Vrasha
Marchitto, Lorie
Doepker, Laura
Ralph, Duncan
Nduati, Ruth
Matsen, Frederick A
Finzi, Andrés
Overbaugh, Julie
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
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.
Citation
Yaffe ZA, Ding S, Sung K, Chohan V, Marchitto L, Doepker L, Ralph D, Nduati R, Matsen FA 4th, Finzi A, Overbaugh J. Reconstruction of a polyclonal ADCC antibody repertoire from an HIV-1 non-transmitting mother. iScience. 2023 Apr 26;26(5):106762. doi: 10.1016/j.isci.2023.106762. PMID: 37216090; PMCID: PMC10196594.Publisher
University of Nairobi
Collections
- Faculty of Health Sciences (FHS) [10378]