A cytotoxic-skewed immune set point predicts low neutralizing antibody levels after Zika virus infection
Elizabeth E. McCarthy,
Pamela M. Odorizzi,
Emma Lutz,
Carolyn P. Smullin,
Iliana Tenvooren,
Mars Stone,
Graham Simmons,
Peter W. Hunt,
Margaret E. Feeney,
Philip J. Norris,
Michael P. Busch,
Matthew H. Spitzer,
Rachel L. Rutishauser
Affiliations
Elizabeth E. McCarthy
Departments of Otolaryngology-Head and Neck Surgery and Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA
Pamela M. Odorizzi
Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA
Emma Lutz
Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA
Carolyn P. Smullin
Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA
Iliana Tenvooren
Departments of Otolaryngology-Head and Neck Surgery and Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA
Mars Stone
Vitalant Research Institute, San Francisco, CA 94104, USA; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA
Graham Simmons
Vitalant Research Institute, San Francisco, CA 94104, USA; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA
Peter W. Hunt
Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA
Margaret E. Feeney
Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA 94110, USA
Philip J. Norris
Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA; Vitalant Research Institute, San Francisco, CA 94104, USA; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA
Michael P. Busch
Vitalant Research Institute, San Francisco, CA 94104, USA; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA
Matthew H. Spitzer
Departments of Otolaryngology-Head and Neck Surgery and Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute for Genomic Immunology, San Francisco, CA 94158, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Corresponding author
Rachel L. Rutishauser
Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA; Gladstone-UCSF Institute for Genomic Immunology, San Francisco, CA 94158, USA; Corresponding author
Summary: Although generating high neutralizing antibody levels is a key component of protective immunity after acute viral infection or vaccination, little is known about why some individuals generate high versus low neutralizing antibody titers. Here, we leverage the high-dimensional single-cell profiling capacity of mass cytometry to characterize the longitudinal cellular immune response to Zika virus (ZIKV) infection in viremic blood donors in Puerto Rico. During acute ZIKV infection, we identify widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated cell types during acute infection are associated with high titers of ZIKV neutralizing antibodies 6 months post-infection, while stable immune features suggesting a cytotoxic-skewed immune set point are associated with low titers. Our study offers insight into the coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials aimed at inducing high levels of antiviral neutralizing antibodies.
