A first-inhuman phase I trial of Vvax001, an alphavirusbased therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 Â 10 5 to 2.5 Â 10 8 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4 + and CD8 + T cell responses against E6 and E7 antigens. Even the lowest dose of 5 Â 10 5 infectious particles elicited E6/E7-specific interferon (IFN)-g responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies.
We present a study of biopsies taken from skin lesions of 44 patients presenting with primary or secondary syphilis. In most primary lesions erosion or, more often, ulceration was present, with a dense inflammatory infiltrate. In secondary syphilis a wide variety of histological changes was present. Blood vessels were frequently involved, with marked endothelial swelling and often proliferation. Treponemes were demonstrated with the Steiner staining method in all investigated cases of primary syphilis and in 71% of secondary syphilis cases. Treponemes were present throughout the dermis, particularly perivascularly, and in the dermal-epidermal junction zone. In two specimens of secondary syphilis treponemes were located predominantly in the epidermis, but there were always some microorganisms demonstrable in the dermis. The inflammatory infiltrate was often located in a perivascular coat-sleeve-like arrangement. In this study plasma cells and lymphocytes were present in all specimens of primary and secondary syphilis. Syphilitic lesions differed from yaws lesions mostly in the location of treponemes and the affection of blood vessels. In this histopathological study of early syphilis, treponemes did not show the epidermiotropic character of yaws, and blood vessel changes were more pronounced than in yaws. Unfortunately, due to the protean histopathological manifestations described in venereal syphilis and in yaws, these two treponemal diseases cannot always be differentiated on histological grounds alone.
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