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Joseph, A., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Louria-Hayon, I., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Plis-Finarov, A., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Zeira, E., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Zakay-Rones, Z., Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
Raz, E., Department of Medicine, University of California San Diego, San Diego, CA 92093, United States
Hayashi, T., Department of Medicine, University of California San Diego, San Diego, CA 92093, United States
Takabayashi, K., Department of Medicine, University of California San Diego, San Diego, CA 92093, United States
Barenholz, Y., Laboratory of Membrane and Liposome Research, Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
Kedar, E., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Synthetic oligodeoxynucleotides (ODNs) containing immunostimulatory sequences (ISS-ODN, also known as CpG-ODNs) have been shown to display in experimental models potent Th1-biassed immunoadjuvant activity upon parenteral or mucosal co-administration with a variety of antigens. In an attempt to potentiate adjuvant activity, and to reduce dose and number of administrations, ISS-ODN was entrapped (up to 90% efficiency) in large (1.5 μm) multilamellar liposomes using a simple and fast (5 min) procedure. Mice were vaccinated once or twice intramuscularly (i.m.) or intranasally (i.n.) with subunit influenza vaccines (consisting of the viral hemagglutinin and neuraminidase, HN) or with hepatitis B surface antigen particles (HBsAg), either non-encapsulated or liposome-encapsulated, together with free or liposomal ISS-ODN (5-25 μg per dose). At 3-12 weeks post-vaccination, the humoral (systemic, mucosal) and cellular responses and protective immunity were assessed. Vaccine formulations containing liposomal ISS-ODN co-administered with either soluble antigen or liposomal antigen (in the same vesicles or in separate vesicles) were up to 30 times more effective than formulations containing un-encapsulated ISS-ODN in inducing: (a) antigen-specific serum and mucosal IgG2a and IgA antibodies; (b) splenocyte proliferative response, cytotoxic activity and IFNγ production; (c) a DTH response; and (d) protection against virus challenge. The response was Th1-dominant in the influenza model and a mixed Th1 + Th2 response in the hepatitis B model. No adverse reactions were noted. Thus, liposomal encapsulation of ISS-ODN further enhances its inherent adjuvant activity. © 2002 Elsevier Science Ltd. All rights reserved.
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הספר "אוצר וולקני"
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תנאי שימוש
Liposomal immunostimulatory DNA sequence (ISS-ODN): An efficient parenteral and mucosal adjuvant for influenza and hepatitis B vaccines
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Joseph, A., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Louria-Hayon, I., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Plis-Finarov, A., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Zeira, E., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Zakay-Rones, Z., Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
Raz, E., Department of Medicine, University of California San Diego, San Diego, CA 92093, United States
Hayashi, T., Department of Medicine, University of California San Diego, San Diego, CA 92093, United States
Takabayashi, K., Department of Medicine, University of California San Diego, San Diego, CA 92093, United States
Barenholz, Y., Laboratory of Membrane and Liposome Research, Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
Kedar, E., Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel
Liposomal immunostimulatory DNA sequence (ISS-ODN): An efficient parenteral and mucosal adjuvant for influenza and hepatitis B vaccines
Synthetic oligodeoxynucleotides (ODNs) containing immunostimulatory sequences (ISS-ODN, also known as CpG-ODNs) have been shown to display in experimental models potent Th1-biassed immunoadjuvant activity upon parenteral or mucosal co-administration with a variety of antigens. In an attempt to potentiate adjuvant activity, and to reduce dose and number of administrations, ISS-ODN was entrapped (up to 90% efficiency) in large (1.5 μm) multilamellar liposomes using a simple and fast (5 min) procedure. Mice were vaccinated once or twice intramuscularly (i.m.) or intranasally (i.n.) with subunit influenza vaccines (consisting of the viral hemagglutinin and neuraminidase, HN) or with hepatitis B surface antigen particles (HBsAg), either non-encapsulated or liposome-encapsulated, together with free or liposomal ISS-ODN (5-25 μg per dose). At 3-12 weeks post-vaccination, the humoral (systemic, mucosal) and cellular responses and protective immunity were assessed. Vaccine formulations containing liposomal ISS-ODN co-administered with either soluble antigen or liposomal antigen (in the same vesicles or in separate vesicles) were up to 30 times more effective than formulations containing un-encapsulated ISS-ODN in inducing: (a) antigen-specific serum and mucosal IgG2a and IgA antibodies; (b) splenocyte proliferative response, cytotoxic activity and IFNγ production; (c) a DTH response; and (d) protection against virus challenge. The response was Th1-dominant in the influenza model and a mixed Th1 + Th2 response in the hepatitis B model. No adverse reactions were noted. Thus, liposomal encapsulation of ISS-ODN further enhances its inherent adjuvant activity. © 2002 Elsevier Science Ltd. All rights reserved.
Scientific Publication
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