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Dermatologic Manifestations in Live Attenuated Dengue Vaccines: A Skin Biopsy Study

Session: Poster Abstract Session: Global Infectious Diseases
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background: Dengue fever is an important emerging disease and diffuse maculopapular rash is a characterizing clinical feature.  Human dendritic cells (DC) are known targets for dengue virus (DV) infection and the etiology of the rash is hypothesized to be due to viral replication in DC or an immune mediated response.  However, studies evaluating the presence of DV in dermal DC during wild-type infection and in one volunteer who received live attenuated dengue vaccine have been conflicting.  In previous clinical trials of the TETRAVAX live attenuated tetravalent dengue vaccine (TDV), the majority of Caucasian subjects develop vaccine-induced rash (VIR).  Examining VIR may provide important clues to the pathophysiology of wild-type infection. 

Methods: In subjects without VIR, a single punch biopsy was performed. In vaccinees with VIR, three punch biopsies were done, two from rash site and one from non-rash site.  Light microscopy was used to score the degree of inflammation and presence of Langerhans cells (LC), a subset of DC, by CD1a immunohistochemistry. VIR biopsies were also evaluated by dual immunofluorescence (IF) together with confocal scanning laser microscopy. 2H2 Ab for DV and CD1a for LC were used as double labels to demonstrate viral location. Data for neutralizing antibody response and viremia was collected.

Results: 12 subjects received TDV and 7 received placebo. VIR was found in 10 vaccinees (83.3%) and no placebos. Nine (90%) of those with VIR had inflammation at the rash site, but not at non-rash sites.  All VIR specimens demonstrated presence of DV within the dermis by IF.  In 2 (20%) of subjects DV was detected in dermal DC, all others had extracellular virus.  VIR was associated with viremia in 7(70%) of subjects with VIR, whereas 1 vaccinee without rash had viremia.  Inflammation did not clearly correlate with higher numbers of DC or higher viremia. 

Conclusion: Following TDV, DV is present in the skin of all vaccinees with VIR, which suggests systemic spread of virus. This is supported by the demonstration of viremia in 70% of subjects with VIR. Surprisingly, most DV was extracellular and not found in DC.  VIR may be a clinical indicator of a robust immune response to vaccination. Correlation of VIR with antibody titer is ongoing.

Olha Smolynets, DO1, Kristen Pierce, MD1, Laura Greene, MD2, Sean Diehl, PhD3, Douglas Taatjes, PhD2, Anna Durbin, MD4, Stephen Whitehead, PhD5 and Beth Kirkpatrick, MD6, (1)Infectious Diseases, University of Vermont, FAHC, Burlington, VT, (2)Pathology, University of Vermont, FAHC, Burlington, VT, (3)University of Vermont, FAHC, Burlington, VT, (4)Johns Hopkins Bloomberg School of Public Health, Takoma Park, MD, (5)National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, (6)Univ of Vermont College of Medicine, Burlington, VT


O. Smolynets, None

K. Pierce, None

L. Greene, None

S. Diehl, None

D. Taatjes, None

A. Durbin, None

S. Whitehead, None

B. Kirkpatrick, None

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