Immunotherapy – 2076. A controlled study of delta inulin-adjuvanted honey bee venom immunotherapy

Background

Honey bee (HB) venom immunotherapy (HBVIT) reduces the frequency of immediate generalised reactions (IGR) to subsequent sting by only ~ 80% and in the process induces IGR in many subjects. In influenza vaccine studies delta inulin adjuvant enhanced immunogenicity and provided antigen-sparing without any adverse reactions. In an ongoing double-blinded clinical trial we are studying the benefits of inulin adjuvant for HBVIT.

Methods

Following institutional ethics committee approval, 26 subjects with a history of IGR to HB sting were randomized 2:1 to receive Albey (Stallergenes) HBVIT (100 mcg maintenance) by clustered, semi-rush regime with (gp A) or without (gp B) Advax™ inulin adjuvant (Vaxine Pty Ltd). Specific IgE (sIgE) was measured by CAP, and specific IgG1 and IgG4 by ELISA.

Results

Clinicians remain blinded to patient randomization. Two subjects have withdrawn for personal reasons. One subject had two anaphylactic reactions at 3 and 100ug of venom, was withdrawn and on breaking code was in gp B (no adjuvant). Two other subjects had mild systemic reactions. A major difference between groups is apparent in sIgG4 responses. Both groups showed a peak sIgG4 response at 14 weeks (early maintenance HBVIT). In gp A however, the sIgG4 rise started earlier, the peak response was much higher and after 12 months of maintenance HBVIT, sIgG4 levels were ~3 fold higher by ELISA OD [results mean (SEM); baseline gp A 0.110 (0.032),gp B 0.076 (0.038), peak .gp A .0.822 (0.155), gp B 0.326 ((0.106), 52 weeks gp A 0.453 (0.223) gp B 0.170 (0.059)]. sIgE responses showed a wide scatter with a rise from baseline of similar magnitude but occurring earlier in group A, followed by a progressive fall, [ baseline gp A 0.960 ((0.171), gp B 0.624 (0.138), peak gp A. 1.242 (0.154), gp B 0.888 (0.163), 52 weeks gp A 0.862 (0.243), gp B 0.541 (0.117)]. sIgG1 responses showed a similar pattern.

Conclusions

With the caveat that only surrogate markers have yet been analysed, delta inulin adjuvant appears to enhance the immunogenicity of HBVIT and to favour sIgG4 responses.