Liposomal immunostimulatory DNA sequence (ISS-ODN): an efficient parenteral and mucosal adjuvant for influenza and hepatitis B vaccines.

摘要: Abstract 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 potentiate adjuvant activity, and reduce dose number administrations, ISS-ODN was entrapped (up 90% efficiency) large (1.5 μm) multilamellar liposomes using simple fast (5 min) procedure. Mice were vaccinated once twice intramuscularly (i.m.) intranasally (i.n.) subunit influenza vaccines (consisting the viral hemagglutinin neuraminidase, HN) hepatitis B surface antigen particles (HBsAg), either non-encapsulated liposome-encapsulated, together free liposomal (5–25 μg per dose). At 3–12 weeks post-vaccination, humoral (systemic, mucosal) cellular responses protective immunity assessed. Vaccine formulations co-administered soluble (in same vesicles separate vesicles) up 30 times more effective than un-encapsulated inducing: (a) antigen-specific serum IgG2a IgA antibodies; (b) splenocyte proliferative response, cytotoxic IFNγ production; (c) DTH response; (d) protection against virus challenge. The response Th1-dominant model mixed Th1+Th2 model. No adverse reactions noted. Thus, encapsulation further enhances its inherent activity.