Pharmaceutical and preclinical evaluation of Advax adjuvant as a dose-sparing strategy for ant venom immunotherapy

dc.contributor.author Wanandy, Troy en_US
dc.contributor.author Honda-Okubo, Yoshikazu en_US
dc.contributor.author Davies, Noel W en_US
dc.contributor.author Rose, Hayley E en_US
dc.contributor.author Heddle, Robert John en_US
dc.contributor.author Brown, Simon G A en_US
dc.contributor.author Woodman, Richard John en_US
dc.contributor.author Petrovsky, Nikolai en_US
dc.contributor.author Wiese, Michael D en_US
dc.date.accessioned 2019-04-29T00:34:51Z
dc.date.available 2019-04-29T00:34:51Z
dc.date.issued 2019-04-09
dc.description © 2019 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (April 2019) in accordance with the publisher’s archiving policy en_US
dc.description.abstract A major challenge in broader clinical application of Jack Jumper ant venom immunotherapy (JJA VIT) is the scarcity of ant venom which needs to be manually harvested from wild ants. Adjuvants are commonly used for antigen sparing in other vaccines, and thereby could potentially have major benefits to extend JJA supplies if they were to similarly enhance JJA VIT immunogenicity. The purpose of this study was to evaluate the physicochemical and microbiological stability and murine immunogenicity of low-dose JJA VIT formulated with a novel polysaccharide adjuvant referred to as delta inulin or Advax™. Jack Jumper ant venom (JJAV) protein stability was assessed by UPLC-UV, SDS-PAGE, SDS-PAGE immunoblot, and ELISA inhibition. Diffraction light scattering was used to assess particle size distribution of Advax; pH and benzyl alcohol quantification by UPLC-UV were used to assess the physicochemical stability of JJAV diluent, and endotoxin content and preservative efficacy test was used to investigate the microbiological properties of the adjuvanted VIT formulation. To assess the effect of adjuvant on JJA venom immunogenicity, mice were immunised four times with JJAV alone or formulated with Advax adjuvant. JJA VIT formulated with Advax was found to be physicochemically and microbiologically stable for at least 2 days when stored at 4 and 25 °C with a trend for an increase in allergenic potency observed beyond 2 days of storage. Low-dose JJAV formulated with Advax adjuvant induced significantly higher JJAV-specific IgG than a 5-fold higher dose of JJAV alone, consistent with a powerful allergen-sparing effect. The pharmaceutical data provides important guidance on the formulation, storage and use of JJA VIT formulated with Advax adjuvant, with the murine immunogenicity studies providing a strong rationale for a planned clinical trial to test the ability of Advax adjuvant to achieve 4-fold JJAV dose sparing in JJA-allergic human patients. en_US
dc.identifier.citation Wanandy, T., Honda-Okubo, Y., Davies, N. W., Rose, H. E., Heddle, R. J., Brown, S. G. A., … Wiese, M. D. (2019). Pharmaceutical and preclinical evaluation of Advax adjuvant as a dose-sparing strategy for ant venom immunotherapy. Journal of Pharmaceutical and Biomedical Analysis, 172, 1–8. https://doi.org/10.1016/j.jpba.2019.04.017 en_US
dc.identifier.doi https://doi.org/10.1016/j.jpba.2019.04.017 en_US
dc.identifier.issn 0731-7085
dc.identifier.uri http://hdl.handle.net/2328/39169
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.rights © 2019 Elsevier B.V. en_US
dc.rights.holder Elsevier B.V. en_US
dc.rights.license CC-BY-NC-ND
dc.subject Adjuvants en_US
dc.subject Advax en_US
dc.subject Allergy en_US
dc.subject Delta inulin en_US
dc.subject Venom immunotherapy en_US
dc.title Pharmaceutical and preclinical evaluation of Advax adjuvant as a dose-sparing strategy for ant venom immunotherapy en_US
dc.type Article en_US
local.contributor.authorOrcidLookup Wanandy, Troy: https://orcid.org/0000-0003-4703-0488 en_US
local.contributor.authorOrcidLookup Petrovsky, Nikolai: https://orcid.org/0000-0002-1580-5245 en_US
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