Strother Camilla, Bouffard Nicole, Smolynets Olha, Graham Nancy R, Elko Evan A, Sabundayo Beulah, Durbin Anna P, Whitehead Stephen S, Taatjes Douglas J, Kirkpatrick Beth D, Greene Laura, Pierce Kristen K, Diehl Sean A
Department of Microbiology and Molecular Genetics, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA; Vaccine Testing Center, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Department of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA; Microscopy Imaging Center, Center for Biomedical Shared Resources, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
J Invest Dermatol. 2024 Dec 27. doi: 10.1016/j.jid.2024.11.015.
Vaccination with the tetravalent live-attenuated dengue virus (DENV) vaccines TV003 and TV005 causes a mild, relatively localized erythematous maculopapular skin rash in most dengue-naïve vaccinees. Human challenge model DENV strains, DENV2Δ30 and DENV3Δ30, trigger a confluent skin rash over most of the body in most unvaccinated participants. To determine the etiology of these rashes, we performed in situ hybridization for DENV genome and assessed cellular infiltration by H&E staining in skin biopsies from humans infected with live-attenuated dengue vaccine DENV2Δ30 or DENV3Δ30 challenge strains. Sixty-three biopsies from 40 participants were included in the study, of which 43 biopsies from 32 patients contained intact RNA. Of these, 1 sample taken from a nonerythematous site from a DENV2Δ30-infected participant experiencing a rash was positive for DENV2 genome. Incidence and severity of lymphocytic infiltration were highest in rash biopsy samples than in those from noninvolved areas in participants experiencing a rash or from those taken from participants not experiencing a rash. These results indicate that the rash associated with infection with live-attenuated dengue vaccines or challenge strains is predominantly lymphocyte-driven perivascular dermal inflammation without local concomitant active viral replication.
用四价减毒活登革病毒（DENV）疫苗TV003和TV005进行接种，在大多数初次接触登革病毒的疫苗接种者中会引发轻微、相对局限的红斑丘疹性皮疹。人攻毒模型登革病毒株DENV2Δ30和DENV3Δ30在大多数未接种疫苗的参与者身上会引发全身大部分区域的融合性皮疹。为了确定这些皮疹的病因，我们对登革病毒基因组进行了原位杂交，并通过苏木精和伊红（H&E）染色评估了感染减毒活登革疫苗DENV2Δ30或DENV3Δ30攻毒株的人类皮肤活检组织中的细胞浸润情况。该研究纳入了40名参与者的63份活检组织，其中32名患者的43份活检组织含有完整RNA。在这些样本中，从一名出现皮疹的DENV2Δ30感染参与者的非红斑部位采集的1份样本登革病毒2型基因组呈阳性。在出现皮疹的参与者的皮疹活检样本中，淋巴细胞浸润的发生率和严重程度高于未出现皮疹的参与者的非受累区域样本或未出现皮疹的参与者的样本。这些结果表明，与减毒活登革疫苗或攻毒株感染相关的皮疹主要是淋巴细胞驱动的血管周围皮肤炎症，没有局部伴随的活跃病毒复制。
