University of California, San Francisco (UCSF) - Departments of Otolaryngology-Head and Neck Surgery and of Microbiology and Immunology; Gladstone-UCSF Institute for Genomic Immunology; University of California, San Francisco (UCSF); Parker Institute for Cancer Immunotherapy; Stanford University - Chan Zuckerberg Biohub
Although the generation of 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. We leveraged 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 identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated cell types during acute infection were associated with high titers of ZIKV neutralizing antibodies 6 months post-infection, while stable immune features suggesting a cytotoxic-skewed immune set point were 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.
McCarthy, Elizabeth E. and Odorizzi, Pamela and Lutz, Emma and Smullin, Carolyn and Tenvooren, Iliana and Stone, Mars and Simmons, Graham and Hunt, Peter and Feeney, Margo and Norris, Philip and Busch, Michael and Spitzer, Matthew H. and Rutishauser, Rachel L., A Cytotoxic-Skewed Immune Set Point Predicts Low Neutralizing Antibody Levels After Zika Virus Infection. Available at SSRN: https://ssrn.com/abstract=4032072 or http://dx.doi.org/10.2139/ssrn.4032072
This version of the paper has not been formally peer reviewed.
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