Infectious Disease Research Institute

About: Infectious Disease Research Institute is a nonprofit organization based out in Seattle, Washington, United States. It is known for research contribution in the topics: Mycobacterium tuberculosis & Adjuvant. The organization has 437 authors who have published 837 publications receiving 33641 citations.

Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major.

Abstract: CD4+ T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4+ T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4+ T cells simultaneously producing interferon-gamma, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-gamma. These data show that the quality of a CD4+ T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (TH1) cells.

Key roles of adjuvants in modern vaccines

Abstract: Vaccines containing novel adjuvant formulations are increasingly reaching advanced development and licensing stages, providing new tools to fill previously unmet clinical needs. However, many adjuvants fail during product development owing to factors such as manufacturability, stability, lack of effectiveness, unacceptable levels of tolerability or safety concerns. This Review outlines the potential benefits of adjuvants in current and future vaccines and describes the importance of formulation and mechanisms of action of adjuvants. Moreover, we emphasize safety considerations and other crucial aspects in the clinical development of effective adjuvants that will help facilitate effective next-generation vaccines against devastating infectious diseases.

Bacterial flagellin is a dominant antigen in Crohn disease

Abstract: Chronic intestinal inflammation, as seen in inflammatory bowel disease (IBD), results from an aberrant and poorly understood mucosal immune response to the microbiota of the gastrointestinal tract in genetically susceptible individuals. Here we used serological expression cloning to identify commensal bacterial proteins that could contribute to the pathogenesis of IBD. The dominant antigens identified were flagellins, molecules known to activate innate immunity via Toll-like receptor 5 (TLR5), and critical targets of the acquired immune system in host defense. Multiple strains of colitic mice had elevated serum anti-flagellin IgG2a responses and Th1 T cell responses to flagellin. In addition, flagellin-specific CD4(+) T cells induced severe colitis when adoptively transferred into naive SCID mice. Serum IgG to these flagellins, but not to the dissimilar Salmonella muenchen flagellin, was elevated in patients with Crohn disease, but not in patients with ulcerative colitis or in controls. These results identify flagellins as a class of immunodominant antigens that stimulate pathogenic intestinal immune reactions in genetically diverse hosts and suggest new avenues for the diagnosis and antigen-directed therapy of patients with IBD.

Genetic Structures at the Origin of Acquisition of the β-Lactamase blaKPC Gene

Abstract: Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A bla KPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece. The bla KPC genes were associated in all cases with transposon-related structures. In the K. pneumoniae YC isolate from the United States, the β-lactamase bla KPC-2 gene was located on a novel Tn 3 -based transposon, Tn 4401 . Tn 4401 was 10 kb in size, was delimited by two 39-bp imperfect inverted repeat sequences, and harbored, in addition to the β-lactamase bla KPC-2 gene, a transposase gene, a resolvase gene, and two novel insertion sequences, IS Kpn6 and IS Kpn7 . Tn 4401 has been identified in all isolates. However, two isoforms of this transposon were found: Tn 4401 a was found in K. pneumoniae YC and K. pneumoniae GR from the United States and Greece, respectively, and differed by a 100-bp deletion, located just upstream of the bla KPC-2 gene, compared to the sequence of Tn 4401 b, which was found in the Colombian isolates. In all isolates tested, Tn 4401 was flanked by a 5-bp target site duplication, the signature of a recent transposition event, and was inserted in different open reading frames located on plasmids that varied in size and nature. Tn 4401 is likely at the origin of carbapenem-hydrolyzing β-lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.