Jill Ekström

Increased immunogenicity of a non-amphipathic protein (BSA) after inclusion into iscoms

Bovine serum albumin (BSA) was used as a non-amphipathic model protein to be included into iscoms. Pretreatment at an acidic pH (2.5) was used to reveal hydrophobic regions, after which BSA could be integrated. In immunization experiments in mice the BSA iscoms induced long lasting and considerably higher serum antibody responses than non-treated monomeric BSA or BSA aggregated by acidic treatment.

Induction of antibody responses in the common mucosal immune system by respiratory syncytical virus immunostimulating complexes.

Abstract Immunostimulating complexes (ISCOMs) containing envelope proteins of respiratory syncytial virus (RSV) were explored as a mucosal delivery system for the capacity of inducing a common mucosal antibody response. Two intranasal (i.n.) administrations of BALB/c mice with ISCOMs induced potent serum IgG, and strong IgA responses to RSV locally in the lungs and the upper respiratory, and remotely in the genital and the intestinal tracts. Virtually no measurable IgA response was found in these mucosal organs after two subcutaneous (s.c.) immunizations. Virus neutralizing (VN) antibodies were detected in serum and in all of the mucosal organ extracts after both s.c. and i.n. immunizations indicating that the neutralizing epitopes were preserved after both mucosal and parenteral modes of administration. While the mucosal IgA response appears to be of mucosal origin, the IgG antibodies to RSV detected in the mucosal organs were likely of serum origin. However, the mucosal VN antibodies correlated with the IgG rather than the IgA levels. An enhanced IgA response to gp120 in various mucosal organs was recorded after i.n. immunization with gp120 incorporated in RSV ISCOMs, indicating a role of RSV envelope proteins in enhancing and targeting mucosal responses to passenger antigens.

Iscom and iscom-matrix enhance by intranasal route the IgA responses to OVA and rCTB in local and remote mucosal secretions.

Iscoms, with rCTB incorporated via the GM1 receptor, enhanced in mice the mucosal immunogenicity of rCTB as antigen after intranasal (i.n.) administration both by inducing IgA response in the remote intestinal tract mucosa and by a 100-fold increase of the specific IgA locally in the lungs. Iscom-matrix as a separate entity mixed with rCTB enhanced the rCTB-IgA response similarly. While OVA in iscoms induced high mucosal IgA responses, iscom-matrix co-administered with OVA induced low or no mucosal IgA response to OVA. A synergism between iscoms and rCTB could only be seen as an adjuvant targeting effect enhancing the IgA response to OVA in the remote genital tract mucosa. In serum, the immunomodulatory effect of iscoms after i.n. administration was seen as an enhanced serum IgG2a response.

An immune stimulating complex (ISCOM) subunit rabies vaccine protects dogs and mice against street rabies challenge

Dogs and mice were immunized with either a rabies glycoprotein subunit vaccine incorporated into an immune stimulating complex (ISCOM) or a commercial human diploid cell vaccine (HDCV) prepared from a Pitman Moore (PM) rabies vaccine strain. Pre-exposure vaccination of mice with two intraperitoneal (i.p.) doses of 360 ng ISCOM or 0.5 ml HDCV protected 95% (38/40) and 90% (36/40) of mice, respectively, against a lethal intracerebral (i.c.) dose with challenge virus strain (CVS). One 360 ng i.p. dose of ISCOM protected 87.5% (35/40) of mice against i.c. challenge with CVS. Three groups of five dogs were vaccinated intramuscularly (i.m.) with 730 ng of rabies ISCOM prepared from either the PM or the CVS rabies strains, and they resisted lethal street rabies challenge. Postexposure treatment of mice with three or four 120 ng i.m. doses of ISCOM protected 90% (27/30) and 94% (45/48), respectively, of mice inoculated in the footpad with street rabies virus, but three doses of HDCV conferred no protection. When four doses of HDCV were administered postexposure, 78% (32/41) of the mice died of anaphylactic shock; 21% (11/52) of mice had already died of rabies 4 days after the third vaccine dose was administered.