Non-pathogenic Borrelia burgdorferi expressing Treponema pallidum TprK and Tp0435 antigens as a novel approach to evaluate syphilis vaccine candidates

Background

Syphilis is resurgent in many developed countries and still prevalent in developing nations. Current and future control campaigns would benefit from the development of a vaccine, but although promising vaccine candidates were identified among the putative surface-exposed integral outer membrane proteins of the syphilis spirochete, immunization experiments in the rabbit model using recombinant antigens have failed to fully protect animals upon infectious challenge. We speculated that such recombinant immunogens, purified under denaturing conditions from Escherichia coli prior to immunization might not necessarily harbor their original structure, and hypothesized that enhanced protection would result from performing similar immunization/challenge experiments with native antigens.

Linear amyopathic dermatomyositis with calcinosis cutis responsive to topical sodium thiosulfate

A case of a 15‐year‐old male patient with a 3‐year history of linear, segmental amyopathic dermatomyositis with calcinosis cutis is presented. The calcinosis was recalcitrant to treatment with topical steroids and hydroxychloroquine. Topical 10% sodium thiosulfate use for 8 weeks resulted in improvement. The use of topical sodium thiosulfate for patients in whom surgical extraction is not an option is detailed.     

Gene Deletions in Mycobacterium bovis BCG Stimulate Increased CD8+ T Cell Responses

Mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host''s immune response. It has been suggested that mycobacteria may contain genes that reduce the host''s ability to elicit CD8⁺ T cell responses. We screened 3,290 mutant Mycobacterium bovis bacillus Calmette Guerin (BCG) strains to identify genes that decrease major histocompatibility complex (MHC) class I presentation of mycobacterium-encoded epitope peptides. Through our analysis, we identified 16 mutant BCG strains that generated increased transgene product-specific CD8⁺ T cell responses. The genes disrupted in these mutant strains had disparate predicted functions. Reconstruction of strains via targeted deletion of genes identified in the screen recapitulated the enhanced immunogenicity phenotype of the original mutant strains. When we introduced the simian immunodeficiency virus (SIV) gag gene into several of these novel BCG strains, we observed enhanced SIV Gag-specific CD8⁺ T cell responses in vivo. This study demonstrates that mycobacteria carry numerous genes that act to dampen CD8⁺ T cell responses and suggests that genetic modification of these genes may generate a novel group of recombinant BCG strains capable of serving as more effective and immunogenic vaccine vectors.