In order to demonstrate that loss of protective effects of partic

In order to demonstrate that loss of protective effects of particular HLA alleles are attributable to accumulation of CTL escape mutations in the population, it is necessary to define

CTL epitopes restricted by common HLA class I alleles in Japan systematically, and to identify escape mutations from those CTL responses. In spite of these limitations, the present study is valuable in consolidating the loss of predominance of some HLA class I alleles in a given population, and in raising concerns about both designing globally effective HIV vaccines and the future virulence of HIV-1. The authors declare no conflicts of interest related to this study. We Barasertib molecular weight thank the patients and clinical staff at the Research Hospital of the Institute of Medical Science, University of Tokyo, for

their essential contributions to this research study. We also thank M. Motose for technical assistance. This work was supported in part by the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases of the Ministry of Education, Culture, Sports, Science and Technology (MEXT); Global COE Program (Center of Education and Research for Advanced Genome-Based Medicine) of MEXT; Grants for Research on HIV/AIDS and Research on Publicly Essential Drugs and Medical Devices from the Ministry of Health, Labor, and Welfare of Japan. “
“Heat-shock proteins (hsp) provide a natural link between innate and adaptive immune responses by combining the ideal properties of antigen carriage (chaperoning), targeting and activation either of antigen-presenting cells (APC), including dendritic cells (DC). Targeting is achieved through binding of hsp to distinct cell surface receptors and is followed by antigen internalization, processing and presentation. An improved understanding of the interaction of hsp with DC has driven the development of numerous hsp-containing

vaccines, designed to deliver antigens directly to DC. Studies in mice have shown that for cancers, such vaccines generate impressive immune responses and protection from tumour challenge. However, translation to human use, as for many experimental immunotherapies, has been slow partly because of the need to perform trials in patients with advanced cancers, where demonstration of efficacy is challenging. Recently, the properties of hsp have been used for development of prophylactic vaccines against infectious diseases including tuberculosis and meningitis. These hsp-based vaccines, in the form of pathogen-derived hsp–antigen complexes, or recombinant hsp combined with selected antigens in vitro, offer an innovative approach against challenging diseases where broad antigen coverage is critical.

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