Improved HIV-positive infant survival is correlated with high levels of HIV-specific ADCC activity in multiple cohorts

Zak A. Yaffe; Nicole E. Naiman; Jennifer Slyker; Bruce D. Wines; Barbra A. Richardson; P. Mark Hogarth; Rose Bosire; Carey Farquhar; Dorothy Mbori Ngacha; Ruth Nduati; Grace John-Stewart; Julie Overbaugh

Cell Reports Medicine (Apr 2021)

Improved HIV-positive infant survival is correlated with high levels of HIV-specific ADCC activity in multiple cohorts

Zak A. Yaffe,
Nicole E. Naiman,
Jennifer Slyker,
Bruce D. Wines,
Barbra A. Richardson,
P. Mark Hogarth,
Rose Bosire,
Carey Farquhar,
Dorothy Mbori Ngacha,
Ruth Nduati,
Grace John-Stewart,
Julie Overbaugh

Affiliations

Zak A. Yaffe: Human Biology Division, Fred Hutchinson Cancer Research 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
Nicole E. Naiman: Human Biology Division, Fred Hutchinson Cancer Research 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
Jennifer Slyker: Department of Global Health, University of Washington, 325 9th Avenue, Seattle, WA 98104, USA; Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA
Bruce D. Wines: Immune Therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia
Barbra A. Richardson: Department of Global Health, University of Washington, 325 9th Avenue, Seattle, WA 98104, USA; Department of Biostatistics, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA
P. Mark Hogarth: Immune Therapies Laboratory, Burnet Institute, Melbourne, VIC, Australia; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia
Rose Bosire: Centre for Public Health Research, Kenya Medical Research Institute, 20752-00202 Nairobi, Kenya
Carey Farquhar: Department of Global Health, University of Washington, 325 9th Avenue, Seattle, WA 98104, USA; Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA
Dorothy Mbori Ngacha: HIV Section, United Nations Children’s Fund, 3 United Nations Plaza, New York, NY 10017, USA; Department of Paediatrics and Child Health, University of Nairobi, Kenyatta National Hospital, Nairobi, Kenya
Ruth Nduati: Department of Paediatrics and Child Health, University of Nairobi, Kenyatta National Hospital, Nairobi, Kenya
Grace John-Stewart: Department of Global Health, University of Washington, 325 9th Avenue, Seattle, WA 98104, USA; Department of Epidemiology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Department of Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Department of Pediatrics, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA
Julie Overbaugh: Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA; Corresponding author

Journal volume & issue: Vol. 2, no. 4
p. 100254

Abstract

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Summary: Defining immune responses that protect humans against diverse HIV strains has been elusive. Studying correlates of protection from mother-to-child transmission provides a benchmark for HIV vaccine protection because passively transferred HIV antibodies are present during infant exposure to HIV through breast milk. A previous study by our group illustrated that passively acquired antibody-dependent cellular cytotoxicity (ADCC) activity is associated with improved infant survival whereas neutralization is not. Here, we show, in another cohort and with two effector measures, that passively acquired ADCC antibodies correlate with infant survival. In combined analyses of data from both cohorts, there are highly statistically significant associations between higher infant survival and passively acquired ADCC levels (p = 0.029) as well as dimeric FcγRIIa (p = 0.002) or dimeric FcγRIIIa binding (p < 0.001). These results suggest that natural killer (NK) cell- and monocyte antibody-mediated effector functions may contribute to the observed survival benefit and support a role of pre-existing ADCC-mediating antibodies in clinical outcome.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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