Safety of a proteoliposome fromNeisseria meningitidesas adjuvant for a house dust mite allergy vaccine

Abstract

The proteoliposome (PL) of Neisseria meningitidis serogroup B has been reported as a safe and potent vaccine adjuvant, inducing a T H 1-skewed response. The present study describes a pre-clinical safety evaluation of an allergy therapeutic vaccine candidate based on purified allergens from Dermatophagoides siboney house dust mite and PL as adjuvant, both components adsorbed onto aluminum hydroxide gel. Two separate studies of acute toxicity evaluation were performed in mice and rabbits, and two repeatdose studies were conducted in non-sensitized and allergen-sensitized Balb/c mice, respectively. The study in sensitized mice intends to model a therapeutic setting. Aerosolized allergen challenge was used in both settings to model natural respiratory exposure. In the therapeutic setting, mice were administered with three doses containing 2 lg allergen at weekly intervals [subcutaneous route] and subsequently challenged with aerosolized allergen for 6 consecutive days. Parameters of general toxicity effects were assessed via measures of behavior, body weight, food and water consumption, and macroscopic evaluation of organs. Histological examination of organs and the injection site was performed. Potential immunotoxicity effects at the systemic level were assessed by blood eosinophil counting and serum allergen specific IgE by ELISA The vaccine did not produce general or functional toxic effects of significance, at a dose up to 100 lg allergen per kg body weight. An expected local reaction at the injection site was observed, which could be attributed mostly to the immunological effect of aluminum hydroxide. The models implemented here suggest an acceptable safety profile of this vaccine for testing in clinical trials of allergy immunotherapy. ARTICLE HISTORY

Immunogenicity of a novel anti-allergic vaccine based on house dust mite purified allergens and a combination adjuvant in a murine prophylactic model

“…The findings using this “preventative” model could be predictive of efficacy for a preventative vaccination strategy in humans against HDM allergy, as a promising approach for managing highly prevalent allergic diseases ( 41 ). A previous work that explored the safety of this vaccine preparation has used also a “therapeutic” setting, i.e., administration of the product in previously sensitized mice mimicking the scenery of AIT in humans ( 19 ). However, further work is needed to develop models fully able to predict, not only safety but also AIT efficacy.…”

“…The use of PL as adjuvant in allergen-specific vaccines could be a valuable alternative to the current AIT based on aqueous or alum-absorbed allergen extracts ( 7 , 17 , 18 ). In previous studies, a novel anti-allergic vaccine formulation based on purified allergens from Dermatophagoides siboney house dust mite (HDM) and PL-Alum adjuvant combination was tested in animal models showing no signs of direct toxicity or functional immunoallergic toxicity, at dose levels greatly in excess to those proposed for early phase clinical trials ( 19 ). A major potential benefit provided by this adjuvanted vaccine would be a decrease in the number of injections required for conventional AIT and the treatment length, as well as, the amount of injected allergen, improving its safety ( 13 ).…”