Phase 2 randomized controlled trial of seasonal influenza vaccine shows Advax® delta inulin adjuvant accelerates the humoral anti‐influenza response

Abstract Advax ® is a delta inulin polysaccharide adjuvant shown in animal models to enhance and accelerate influenza vaccine protection. A clinical trial was conducted in 109 healthy adult participants aged 18–70 years randomized to receive a single intramuscular seasonal trivalent influenza vaccine (TIV) alone or formulated with 5 or 10 mg Advax ® adjuvant to explore the effect of the adjuvant on the humoral immune response. The addition of Advax ® 10 mg to TIV accelerated the rise in serum influenza‐specific antibodies, with this group exhibiting significantly higher increases in hemagglutinin inhibition (HAI) against 3 of the 3 vaccine serotypes at 7 days post‐vaccination (7 dpv), 2 at 14 dpv and 1 at 21 dpv. By 7 dpv, the Advax 10‐mg group achieved HAI seroprotection rates of 96.9% against H1N1, 100% against H3N2 and 46.9% against influenza B versus rates of 86.1%, 100% and 22.2%, respectively, for the TIV alone group. The Advax ® ‐adjuvanted groups demonstrated an increased frequency of non‐silent CDR3 mutations in the B cell receptor heavy chain of peripheral blood IgG + and IgM + plasmablasts at 7 dpv, consistent with the adjuvant enhancing B cell affinity maturation in IgM + and IgG + plasmablasts independently of class switch recombination. The ability of Advax adjuvant to accelerate humoral responses against influenza could be advantageous during influenza outbreaks when time to protection is of the essence. Further studies are needed into the mechanisms whereby delta inulin accelerates vaccine immunity.