712 research outputs found
Evaluatie 'Tien jaar terugverdientijd' - Ervaringen met en oordelen over een beslissingsregel voor energiebesparende investeringen in Amsterdamse gemeentelijke gebouwen
Preclinical development of DNA vaccine candidates for the treatment of HPV16 induced malignancies
High-risk Human Papilloma Virus (HPV) induced malignancies are an interesting target for immunotherapy as they invariably express the viral proteins E6 and E7 that allow specific recognition of tumor cells without the risk of inducing autoimmunity. This thesis describes the preclinical development of pDNA vaccine candidates for the treatment of HPV16 induced malignancies. For this purpose gene-shuffled (SH) versions of HPV16 E6 and E7 were used to avoid the risk of transformation at the vaccination site. To improve the immunogenicity of E6SH and E7SH several optimizations strategies were evaluated. First it is shown that genetic fusion with Tetanus Toxin Fragment C (TTFC), results in a dramatic increase in immunogenicity. The resulting vaccine candidates TTFC-E6SH and TTFC-E7SH were also demonstrated to have lost their transforming potential. Secondly it is demonstrated that the mere addition of an endoplasmatic reticulum targeting sequence and a set of promiscuous CD4 helper epitopes results in an enormous increase of the immunogenicity of E6SH and E7SH. This design decreases the risk of raising competing carrier specific immune responses. Finally several nanoparticle based formulations of a model pDNA vaccine were evaluated and it is demonstrated that for in vivo applications it is essential to shield the cationic charge of such nanoparticles.The Netherlands organization for health research and development (ZonMw) grant 432-00-001.UBL - phd migration 201
Standard errors and confidence intervals of norm statistics for educational and psychological tests
Best practice examples of existing economic policy instruments and potential new economic policy instruments to reduce marine litter and eliminate barriers to GES
Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilization syndromes
Life-threatening Pneumocystis jiroveci pneumonia following treatment of severe Cushing's syndrome
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