Immunogenicity and safety of Advax™, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: A randomized controlled Phase 1 study

Abstract

There is a need for additional safe and effective human vaccine adjuvants. Advax is a novel adjuvant produced from semi-crystalline particles of delta inulin. In animal studies Advax enhanced humoral and cellular immunity to hepatitis B surface antigen (HBsAg) without inducing local or systemic reactogenicity. This first-in-man Phase 1 clinical trial tested the safety and tolerability of three intramuscular doses of HBsAg formulated with Advax in a group of healthy adult subjects. Advax was well tolerated with injection site pain scores not significantly different to subjects receiving HBsAg alone and no adverse events were reported in subjects that received Advax. Seroprotection and HBsAb geometric mean titers (GMT) after three immunizations were higher in the Advax 5mg (seroprotection 5/6, 83.3%, GMT 40.7, 95% CI 11.9–139.1) and 10mg (seroprotection 4/5, 80%, GMT 51.6, 95% CI 10.0–266.2) groups versus HBsAg alone (seroprotection 1/5, 20%, GMT 4.1, 95% CI 1.3–12.8). Similarly the proportion of subjects with positive CD4 T-cell responses to HBsAg was higher in the Advax 5mg (4/6, 67%) and Advax 10mg (4/5, 80%) groups versus HBsAg alone (1/5, 20%). These results confirm the safety, tolerability and immunogenicity of Advax adjuvant observed in preclinical studies. Advax may represent a suitable replacement for alum adjuvants in prophylactic human vaccines subject to confirmation of current results in larger studies. Australia and New Zealand Clinical Trial Registry: ACTRN12607000598482

Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

“…It has been shown to improve the immunogenicity and efficacy of a wide variety of vaccines including against influenza, hepatitis B, Japanese encephalitis, West Nile virus, Human immunodeficiency virus, anthrax and Listeria (Dolter et al, 2011, Feinen et al, 2014, Honda-Okubo et al, 2012, Larena et al, 2013, Petrovsky et al, 2013, Rodriguez-Del Rio et al, 2015, Saade et al, 2013). Vaccines containing Advax adjuvant have already been evaluated in human clinical trials, including hepatitis B, influenza and insect-sting allergy vaccines (Gordon et al, 2014, Heddle et al, 2013, Nolan et al, 2008). …”

Physical characterization and in silico modeling of inulin polymer conformation during vaccine adjuvant particle formation

“…This polysaccharide is biocompatible and biodegradable and specific semicrystalline particulate forms of inulin have immunomodulatory properties (Cooper & Petrovsky, 2011). The utility of γ- and δ-inulin isoforms as vaccine adjuvants has been demonstrated in both animal (Feinen, Petrovsky, Verma & Merkel, 2014; Honda-Okubo, Kolpe, Li & Petrovsky, 2014; Saade, Honda-Okubo, Trec & Petrovsky, 2013) and human (Gordon, Kelley, Heinzel, Cooper & Petrovsky, 2014; Gordon, Sajkov, Woodman & Honda-Okubo, 2012) studies. However, to fully realize the vaccine adjuvant benefit of inulin particles there is a need to better understand how inulin polymer chains assemble to form the adjuvant-active inulin particles.…”

Novel approaches for the design, delivery and administration of vaccine technologies

“…The antigen release profile of a PLGA particle can be modified from a couple of days to more than a year [82,83]. Advax, an insulin-derived microparticle, has been used in clinical trials as an adjuvant for hepatitis B, influenza and insectsting allergy vaccines [84][85][86]. Advax, an insulin-derived microparticle, has been used in clinical trials as an adjuvant for hepatitis B, influenza and insectsting allergy vaccines [84][85][86].…”