ArticleEBioMedicine2019
Antibody-dependent cellular cytotoxicity targeting CD4-inducible epitopes predicts mortality in HIV-infected infants.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- A Method for High-Throughput Screening of Monoclonal Antibody Internalization Using a DNA/Protein Molecular Staple.Small methods · 2025Article
- Reconstruction of a polyclonal ADCC antibody repertoire from an HIV-1 non-transmitting mother.iScience · 2023Article
- Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans.NPJ vaccines · 2022Article
- Challenges and Opportunities of Therapies Targeting Early Life Immunity for Pediatric HIV Cure.Frontiers in immunology · 2022Review
- Evolution of Antibodies to Native Trimeric Envelope and Their Fc-Dependent Functions in Untreated and Treated Primary HIV Infection.Journal of virology · 2021Article
- Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidity.Cell reports. Medicine · 2021Article
- Improved HIV-positive infant survival is correlated with high levels of HIV-specific ADCC activity in multiple cohorts.Cell reports. Medicine · 2021Article
- Article
- Effects of gp120 Inner Domain (ID2) Immunogen Doses on Elicitation of Anti-HIV-1 Functional Fc-Effector Response to C1/C2 (Cluster A) Epitopes in Mice.Microorganisms · 2020Article
- Recent insights into Fc-mediated effector responses to HIV-1.Current opinion in HIV and AIDS · 2020Review
- Polyfunctional Fc Dependent Activity of Antibodies to Native Trimeric Envelope in HIV Elite Controllers.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAntibody-dependent cellular cytotoxicity (ADCC) has been associated with improved infant outcome in mother-to-child transmission (MTCT) of HIV-1. Epitopes of these ADCC-mediating antibodies remain unidentified. CD4-inducible (CD4i) epitopes on gp120 are common ADCC targets in natural infection and vaccination. We tested whether CD4i epitope-specific ADCC mediated by maternal antibodies or passively-acquired antibodies in infants is associated with reduced MTCT and improved infant survival.
methodsWe used variants of CD4i cluster A-specific antibodies, A32 and C11, and a cluster C-specific antibody, 17b, with mutations abolishing Fc-Fc receptor interactions as inhibitors in a competition rapid and fluorometric ADCC assay using gp120-coated CEM-nkr target cells with plasma from 51 non-transmitting and 21 transmitting breastfeeding mother-infant pairs.
findingsCluster A-specific ADCC was common. Individually, neither A32-like nor C11-like ADCC was statistically significantly associated with risk of MTCT or infected infant survival. In combination, total maternal cluster A-specific ADCC was statistically significantly associated with decreased infected infant survival in a log-rank test (p = 0·017). There was a non-significant association for infant passively-acquired total cluster A-specific ADCC and decreased infected infant survival (p = 0·14). Surprisingly, plasma ADCC was enhanced in the presence of the defective Fc 17b competitor. Defective Fc 17b competitor-mediated maternal ADCC enhancement was statistically significantly associated with reduced infected infant survival (p = 0·011). A non-significant association was observed for passively-acquired infant ADCC enhancement and decreased survival (p = 0·19). INTERPRETATIONS: These data suggest that ADCC targeting CD4i epitopes is not associated with protection against breast milk HIV transmission but is associated with decreased survival of infected infants. FUND: This study was funded by NIH grant R01AI076105 and NIH fellowship F30AI136636.
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