Enhanced immune response to T-independent antigen by using CpG oligodeoxynucleotides encapsulated in liposomes

Immunostimulatory CpG oligodeoxynucleotides (ODN) have been tested as immun oadjuvants for various vaccines including T-cell independent (TI) antigens. Findings from previous reports suggest that close physical association of CpG ODN to the antigen could enhance its adjuvant effect. As an alternative to chen-deal conjugation of CpG ODN to the antigen, the current study is a imed at determining the benefit of using liposomes as a carrier for CpG ODN to improve the immune response to biotinylated liposomes (Bx-liposomes), a model of a TI antigen. Liposomes with suboptimal concentration of hapten ( 1% biotin) were not immunogenic. However, when CpG ODN encapsulated in Bx-l iposomes were used to immunize mice, a hapten-specific response was obtaine d as indicated by antibody-mediated elimination of re-administered Bx-lipos omes. CpG ODN co-administered with empty Bx-liposomes could not achieve the same effect, indicating the requirement for encapsulation of the adjuvant. Using both intravenous (i.v.) and subcutaneous (s.c.) immunization methods , it was found that IgM levels, but not IgG levels were elevated. Immunizat ion in nude mice confirmed that the immune response obtained was TI. The us e of non-CpG ODN and an ODN with alternatively flanked CpG motifs showed no adjuvant effect. Incorporation of poly(ethylene)glycol (PEG)-modified lipi d in liposomes enhanced the immune response even further. In conclusion, ou r data shows that liposomes are a useful delivery vehicle for CpG ODN as an immune adjuvant for TI antigens. (C) 2001 Elsevier Science Ltd. All rights reserved.