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Randomized controlled trial demonstrating the benefits of delta inulin adjuvanted immunotherapy in patients with bee venom allergy - 05/08/19

Doi : 10.1016/j.jaci.2019.03.035 
Robert Heddle, MBBS, PhD, FRCPA, FRACP a, b, e, Anthony Smith, MBBS, PhD, FRACP c, Richard Woodman, MBiostat, PhD d, Pravin Hissaria, MD, FRACP b, Nikolai Petrovsky, MBBS, PhD, FRACP e, f,
a University of Adelaide, North Terrace, Adelaide, Australia 
b Royal Adelaide Hospital, North Terrace, Adelaide, Australia 
c Allergy and Clinical Immunology Department, Flinders Medical Centre, Bedford Park, Australia 
d Flinders Centre for Epidemiology and Biostatistics, Flinders University, Bedford Park, Australia 
e Flinders University, Bedford Park, Australia 
f Vaxine, Bedford Park, Australia 

Corresponding author: Nikolai Petrovsky, MBBS, PhD, FRACP, Flinders University, Bedford Park SA, Australia 5042.Flinders UniversityBedford Park SA5042Australia

Abstract

Background

Allergic reactions to Hymenoptera insect stings remain a major global clinical problem. Although effective, parenteral desensitization regimens require use of costly venom extracts and require frequent visits over extended periods of time.

Objective

Adjuvants are commonly used to enhance the efficacy of infectious disease vaccines, and this study asked whether Advax (Vaxine Pty Ltd, Adelaide, Australia), a novel noninflammatory polysaccharide adjuvant, might provide similar benefits for allergy desensitization.

Methods

A randomized, controlled phase 1/2 trial was undertaken in 27 adults with a history of rapid-onset systemic allergic reactions to honeybee stings and positive specific IgE levels to evaluate the safety and efficacy of honeybee venom immunotherapy (HBVIT) combined with Advax adjuvant. Venom immunotherapy (VIT) was administered monthly for 30 months after achievement of maintenance doses.

Results

Advax-adjuvanted HBVIT was well tolerated. Around week 14 of VIT, specific IgG4 responses peaked in both groups but increased earlier, peaked higher, and were better maintained through the end of the study in the Advax-adjuvanted arm. Several different patterns of serologic response to VIT were seen; some subjects had a dominant IgG4 response, some had a combined IgG4 and IgG1 response, and some had an exclusively IgG1 response. In some subjects specific IgE levels increased during the induction phase and then decreased, whereas in others specific IgE levels progressively decreased from the start of VIT.

Conclusion

Advax adjuvant favorably enhanced the immunogenicity of HBVIT, with an early and prolonged switch to specific IgG4 production. The ability of Advax adjuvant to enhance VIT efficacy warrants further study.

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Graphical abstract




El texto completo de este artículo está disponible en PDF.

Key words : Hymenoptera, anaphylaxis, immunotherapy, IgG4, inulin, adjuvant, allergy

Abbreviations used : AHBVIT, CRP, HBVIT, MCT, SARS, SHBVIT, VIT, WCC


Esquema


 The study was supported by a grant from the Australian Respiratory and Sleep Medicine Institute. Development of Advax adjuvant was supported by funding from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, under contracts HHSN272200800039C and U01 AI061142, and N.P. is currently supported by contract HHSN272201400053C.
 Disclosure of potential conflict of interest: N. Petrovsky is associated with Vaxine Pty Ltd, which holds intellectual property over Advax adjuvant. The rest of the authors declare that they have no relevant conflicts of interest.
 Australian New Zealand Clinical Trials Registry: ACTRN12608000379314.


© 2019  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 144 - N° 2

P. 504 - août 2019 Regresar al número
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