Sucrose fatty acid sulphate esters as novel vaccine adjuvant.
In search for novel adjuvants for human and veterinary vaccines, we focus on synthetic carbohydrates because microbial carbohydrates function as important alarming signals to the immune system. Mono- and disaccharides were added chemically with various functional groups and adjuvant activity and reactogenicity were determined in parallel. In our test model, we used poor immunogens to identify the most effective adjuvants and non-rodent mammals to facilitate extrapolation to humans. Disaccharides added with both fatty acid and sulphate esters and immobilized on a vehicle exerted high adjuvanticity. Chemical structure and presentation of the compound were optimized for a maximal in vivo performance. The formulation selected for human therapeutic vaccines (designated as 'CoVaccine HT') consists of a sucrose fatty acid sulphate ester immobilized on the oil droplets of a submicron emulsion of squalane-in-water. Both humoral and cell-mediated responses were enhanced in a dosedependent fashion against a wide range of antigens, e.g. inactivated viruses, bacterial subunits, recombinant proteins, virus-like particles and peptide-protein conjugates. Remarkably high booster reactions indicated strong immunological memory established by the first contact between host and antigen in presence of the adjuvant. In comparison with existing adjuvants, CoVaccine HT revealed similar or even higher adjuvanticity than mineral oil emulsions (O/W, W/O or O/W) but significantly lower reactogenicity. We concluded that CoVaccine HT is a promising adjuvant as it combines the efficacy of strong adjuvants with the safety of mild ones, is effective towards various types of antigens in large non-rodent mammals and is a chemically defined, stable, aqueous formulation.
Hilgers
Luuk A T
LA
CoVaccine BV, Edelhertweg 15, 8219 PH Lelystad, The Netherlands. luuk.hilgers@covaccine.com
Blom
Anneke G
AG
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D005227:Fatty Acids / Q000009:adverse effects / Q000494:pharmacology*; D013395:Sucrose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013431:Sulfates / Q000009:adverse effects / Q000494:pharmacology*; D014612:Vaccines / Q000276:immunology
D000276:Adjuvants, Immunologic; D005227:Fatty Acids; D013431:Sulfates; D014612:Vaccines; D013395:Sucrose