Mark K. Slifka, PhD, Donald Y. M

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Presentation transcript:

Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis Mark K. Slifka, PhD, Donald Y.M. Leung, MD, PhD, Erika Hammarlund, MS, Hans-Peter Raué, PhD, Eric L. Simpson, MD, MCR, Susan Tofte, FNP, Shahana Baig-Lewis, MPH, Gloria David, PhD, Henry Lynn, PhD, Rob Woolson, MS, JD, Tissa Hata, MD, Henry Milgrom, MD, Jon Hanifin, MD Journal of Allergy and Clinical Immunology Volume 133, Issue 2, Pages 439-447 (February 2014) DOI: 10.1016/j.jaci.2013.10.037 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Flow diagram of study subjects participating in the trial. SC, Subcutaneous; TC, transcutaneous. Journal of Allergy and Clinical Immunology 2014 133, 439-447DOI: (10.1016/j.jaci.2013.10.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Duration of YFV RNAemia after subcutaneous or transcutaneous vaccination. Kaplan-Meier curves show the proportion of YFV-seroconverted subjects with positive scores for YFV RNA by using RT-PCR during the first 2 weeks after vaccination. The limit of detection was less than 1 plaque-forming unit/mL for serum spiked with purified YFV. NA, Nonatopic; SC, subcutaneous; TC, transcutaneous. TC-AD, n = 18; TC-NA, n = 14; SC-AD, n = 17; and SC-NA, n = 20. Journal of Allergy and Clinical Immunology 2014 133, 439-447DOI: (10.1016/j.jaci.2013.10.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Induction of neutralizing YFV-specific antibody responses after subcutaneous or transcutaneous vaccination. A, At 30 days after YFV vaccination, seroconversion rates were determined for the different vaccine groups and defined as a YFV-specific neutralizing titer of 10 or greater. B, Levels of YFV neutralizing antibody among seropositive subjects were measured based on the LNI in which serum is held constant and different amounts of virus are neutralized. C, Levels of YFV neutralizing antibody among seropositive subjects were measured by determining the serum dilution required to neutralize 50% of viral plaques (held constant at 50-100 YFV plaques). Error bars represent 95% CIs. NA, Nonatopic; SC, subcutaneous; TC, transcutaneous. Journal of Allergy and Clinical Immunology 2014 133, 439-447DOI: (10.1016/j.jaci.2013.10.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Kinetics and magnitude of vaccine-induced YFV-specific CD4+ and CD8+ T-cell responses. The frequency of virus-specific T cells was measured by stimulating PBMCs with purified YFV and measuring the frequency of IFN-γ+TNF-α+ T cells at each time point by using intracellular cytokine staining analysis. A, Representative flow cytometric dot plot showing the virus-specific CD4+ and CD8+ T-cell response after YFV vaccination. The dot plots were pregated on CD4+CD8− and CD4−CD8+ T cells and show the number of events per 106 CD4+ or CD8+ cells after background subtraction (medium alone). B-E, The kinetics and magnitude of YFV-specific CD4+ T cells (Fig 4, B and C) or CD8+ T cells (Fig 4, D and E) were measured in subjects vaccinated through the subcutaneous route (Fig 4, B and D) or the transcutaneous route (Fig 4, C and E). The numbers indicate measured P values at each time point, and error bars represent 95% CIs. NA, Nonatopic. Journal of Allergy and Clinical Immunology 2014 133, 439-447DOI: (10.1016/j.jaci.2013.10.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Comparison between baseline total IgE levels and YFV-induced immune responses. Total serum IgE levels obtained at baseline were compared with subsequent YFV-induced immune responses at 30 days after vaccination and included YFV-specific neutralizing titers (NT50; A and B), YFV-specific CD4+ T-cell responses (C and D), and YFV-specific CD8+ T-cell responses (E and F) in subjects vaccinated through the subcutaneous route (Fig 5, A, C, and E) or the transcutaneous route (Fig 5, B, D, and F). Red symbols represent patients with AD, blue symbols represent nonatopic (NA) subjects, and red or blue ellipses represent 95% CIs. Journal of Allergy and Clinical Immunology 2014 133, 439-447DOI: (10.1016/j.jaci.2013.10.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions