3127 Preclinical Study on the Use of Micro Crystalline Tyrosine (MCT) Adjuvants in Allergy Immunotherapy

Friday, 16 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Alan David Bullimore , Allergy Therapeutics, Worthing, United Kingdom

Matthew Heath, PhD , Allergy Therapeutics, Worthing, United Kingdom

Murray Skinner, PhD , Allergy Therapeutics, Worthing, United Kingdom

BACKGROUND

Vaccines and allergen-specific immunotherapy typically contain adjuvants that facilitate immune responses in humans and animals. For almost a century, salts of aluminium (hydroxide and phosphate) were the only approved adjuvants in humans. One major problem of aluminium adjuvants is that they are not biodegradable and that they typically stimulate so-called T-helper type 2 (Th2) as opposed to Th1 immune responses, which again affects the type of antibody responses produced. The goals of new adjuvants are therefore (i) to facilitate recognition of antigen/allergen, (ii) to be biodegradable and biocompatible, (iii) to be without toxic or inflammatory side effects, and (iv) to trigger protective Th1-like immune responses as well as allergen-neutralising antibodies. Co-precipitates of micro crystalline tyrosine (MCT) and proteins have been suggested as candidate adjuvants for allergen-specific immunotherapy.

METHODS

Immunogenicity testing of MCT-ovalbumin vaccines in naïve BALB/c and C57BL/6 mice was undertaken. Three injections were performed at 2 week intervals, and the mice were tail bled prior to each injection as well as at different time points after the last injection. The obtained sera were analysed for OVA-specific antibodies, while spleen cells were tested for T-cell responses including cytokine secretion after re-stimulation of the cells in vitro with ovalbumin.

RESULTS

MCT has good adjuvant properties, comprising a high adsorptive power for proteins, and enhancement of Th1-like and associated immune responses, highlighting its potential of action as a biodegradable depot adjuvant in allergen-specific immunotherapy. MCT is naturally metabolised and the pharmacokinetics of MCT present a half-life at the injection site of 48 hours; this is a particular benefit for allergy SCIT, a traditionally long course treatment, minimising the need for accumulation of non-biodegradable adjuvant.  

CONCLUSIONS

Results from pre-clinical immunogenicity and MCT mode-of-action studies in mice have demonstrated the potential of MCT as a non-toxic and biodegradable alternative to conventional adjuvants for use in allergen immunotherapy