ISCOMs as delivery systems for mucosal immunization

The overall objective of this thesis is to explore the potential of ISCOMs as mucosal adjuvant and delivery systems. The model consists of ISCOMs containing envelope proteins of respiratory syncytial virus (RSV) as vaccine antigen and targeting molecule, gpl20 of HIV and ovalbum (OVA) as passenger vaccine antigens to be delivered to the mucosal immune system, and CTB as a model antigen and targeting molecule.Intranasal (i.n.) administration ofRSV ISCOMs induced a surprisingly strong and longlasting mucosal IgA response in mice, as well as a high systemic antibody response of a magnitude similar to that of subcutaneous (s.c.) immunization. The mucosal IgA was distributed to the local administrative sites of the upper respiratory tract (URT) and the lungs, but also to the remote mucosal sites of the genital and intestinal tracts. Virus neutralizing (VN) antibody was also detected in serum and in these mucosal organs, and mice were protected against challenge infection.Gpl20 as a passenger antigen in RSV ISCOMs induced by i.n. potent mucosal IgA response in mice at various mucosal sites encompassing the remote genital tract, giving promise for the mucosal delivery concept with a targeting molecule and with passenger antigens, which is e.g. of interest for combating sexually transmitted diseases (STDs).The dual adjuvant targeting system of ISCOMs bearing rCTB-OVA enhanced the mucosal antibody responses both to rCTB and the passenger. This ISCOM combination enhanced mucosal IgA response to OVA in the remote genital tract. ISCOMs complemented the iCTB-induced IgGl response in mice by increasing the IgG2a level known to be promoted by IFN-y, leading to a balanced Thl/Th2 immune response.In conclusion, the present study provides direct evidences that ISCOMs are potent mucosal adjuvant and delivery systems, and promising alternative and complement to CTB, by increasing and modulating the immune response to CTB itself as well as to passenger antigens. The incorporation of a targeting antigen with combinations of adjuvants and passenger antigens in the same ISCOM, creates an attractive approach to modem vaccine design