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Cell Host Microbe. 2015 Apr 8;17(4):500-6. doi: 10.1016/j.chom.2015.03.002.

Passively acquired antibody-dependent cellular cytotoxicity (ADCC) activity in HIV-infected infants is associated with reduced mortality.

Author information

1
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; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
2
Department of Global Health, University of Washington, Seattle, WA 98195, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
3
Department of Global Health, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA; Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
4
Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
5
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.

Abstract

In addition to direct effects on virus infectivity, antibodies mediate antibody-dependent cellular cytotoxicity (ADCC), the killing of an antibody-coated virus-infected cell by cytotoxic effector cells. Although ADCC has been suggested to protect against HIV, the relationship between HIV-specific ADCC antibodies at the time of HIV exposure and infection outcome in humans remains to be assessed. We evaluated the ADCC activity of passively acquired antibodies in infants born to HIV-infected mothers. ADCC levels were higher in uninfected than infected infants, although not significantly. Increase in ADCC antibody activity in infected infants was associated with reduced mortality risk. Infant ADCC positively correlated with the magnitude of IgG1 binding, and IgG1 levels were associated with survival in infected infants. Infant IgG3-binding antibodies were not associated with infected infant survival. These data suggest a therapeutic benefit of pre-existing HIV-specific ADCC antibodies and support a role for eliciting ADCC-mediating IgG1 in HIV vaccines.

PMID:
25856755
PMCID:
PMC4392343
DOI:
10.1016/j.chom.2015.03.002
[Indexed for MEDLINE]
Free PMC Article

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