Targeting prohibitins at the cell surface prevents Th17-mediated autoimmunity.

T helper (Th)17 cells represent a unique subset of CD4+ T cells and are vital for clearance of extracellular pathogens including bacteria and fungi. However, Th17 cells are also involved in orchestrating autoimmunity. By employing quantitative surface proteomics, we found that the evolutionarily conserved prohibitins (PHB1/2) are highly expressed on the surface of both murine and human Th17 cells. Increased expression of PHBs at the cell surface contributed to enhanced CRAF/MAPK activation in Th17 cells. Targeting surface-expressed PHBs on Th17 cells with ligands such as Vi polysaccharide (Typhim vaccine) inhibited CRAF-MAPK pathway, reduced interleukin (IL)-17 expression and ameliorated disease pathology with an increase in FOXP3+-expressing Tregs in an animal model for multiple sclerosis (MS). Interestingly, we detected a CD4+ T cell population with high PHB1 surface expression in blood samples from MS patients in comparison with age- and sex-matched healthy subjects. Our observations suggest a pivotal role for the PHB-CRAF-MAPK signalling axis in regulating the polarization and pathogenicity of Th17 cells and unveil druggable targets in autoimmune disorders such as MS.

Comparative Study of Two Droplet-Based Dissolving Microneedle Fabrication Methods for Skin Vaccination.

Dissolving microneedles (DMNs) have been widely studied in medical applications due to their pain-free administration, superior efficiency, and safe drug delivery. In skin vaccination, preserving the activity of the encapsulated antigen is an important consideration, as antigen activity is lost during DMN fabrication because of various stress factors. These stress factors vary between fabrication methods and each method affects the antigen's activity to different degrees. In this study, the activity of encapsulated antigens delivered by DMNs is compared between two recently developed DMN fabrication methods; droplet-born air blowing (DAB) and centrifugal lithography (CL) for a model scrub typhus vaccine antigen, ScaA. Although the in vitro analysis of ScaA-loaded DMNs (ScaA-DMNs) does not show any differences in physical properties depending on the fabrication methods, the immunogenicity of the CL-produced ScaA-DMN is significantly higher based on cytokine measurement and humoral immunity. DAB and CL differ in their solidification conditions, suggesting that solidification factors critically affect the encapsulated antigen's activity. ScaA-DMNs may also be stably stored for 4 weeks at room temperature. In conclusion, CL is a superior DMN fabrication method compared with DAB, and this study proves that DMN is feasible and practical for skin vaccination.

Enteric fever: an Israeli perspective.

Typhoid fever is no longer endemic to most developed countries, including Israel. When encountered, it usually occurs in travelers returning from endemic countries. Worldwide, the disease is far from being eradicated. It is still highly prevalent in some popular travel destinations such as India. With the continued increase in Israelis traveling to (and in migrant workers arriving from) endemic regions, physicians in Israel should be well acquainted with the disease. Unfortunately, with the limited efficacy of the current typhoid vaccinations and the increase in multidrug-resistant strains, cases among travelers are expected to continue to increase and become ever challenging to treat.

Immunization with a portion of rickettsial outer membrane protein A stimulates protective immunity against spotted fever rickettsiosis.

Two approaches for presentation of a part of the rickettsial outer membrane protein A (OmpA) of Rickettsia rickettsii, namely (1) recombinant Mycobacterium vaccae (rMV) or (2) recombinant DNA vaccine, stimulated protective immunity against a lethal challenge with the closely related bacterium, R. conorii, in mice. After primary immunization with rMV and booster immunization with homologous recombinant protein, 67 and 55% of mice were protected against challenge in two experiments. DNA vaccination with booster recombinant protein immunization protected six out of eight animals from a lethal challenge. Production of IFN-gamma by antigen-exposed T-lymphocytes of DNA vaccine recipients indicated that cellular immunity had been stimulated.

Vacunas contra rickettsias / Vaccines against rickettsias

Las rickettsias son transmitidas por la picadura de garrapatas y ácaros infectados o por la contaminación de la piel o membranas mucosas con heces de piojos o pulgas. La epidemiología se presenta en varias enfermedades: tifo epidémico, tifo murino, tifo escrofular, fiebre manchada de las montañas rocallosas y fiebre Q. En el aspecto histórico de las vacunas anti-rickettsiales, observando retrospectivamente, se concluye que el fracaso de esos intentos -iniciados antes de 1940- no es sorprendente dada la heterogeneidad antigénica de las cepas de esta especie. Los esfuerzos actuales para el desarrollo de las vacunas anti-rickettsiales están enfocados en la clonación de los genes que codifican para la proteína R. prowaseki; producirla mediante la tecnología del DNA recombinante y evaluar la proteína así expresada como probable vacuna. Aunque tales enfoque novedosos son prometedores, la prueba definitiva de eficiencia es la capacidad de la vacuna para proteger humanos expuestos a la infección con rickettsias