MAS-1, a novel water-in-oil adjuvant/delivery system, with reduced seasonal influenza vaccine hemagglutinin dose may enhance potency, durability and cross-reactivity of antibody responses in the elderly.

Background: Increased influenza vaccine efficacy is needed in the elderly at high-risk for morbidity and mortality due to influenza infection. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets.
Methods: A phase 1, randomized, double-blind, safety and immunogenicity, adjuvant dose escalation trial was conducted in persons aged 65 years and older. MAS-1 adjuvant dose volumes at 0.3 mL or 0.5 mL containing 9 µg per HA derived from licensed seasonal trivalent influenza vaccine (IIV, Fluzone HD 60 µg per HA, Sanofi Pasteur) were compared to high dose (HD) IIV (Fluzone HD). Safety was measured by reactogenicity, adverse events, and safety laboratory measures. Immunogenicity was assessed by serum hemagglutination inhibition (HAI) antibody titers.
Results: Forty-five subjects, aged 65-83 years, were randomly assigned to receive 9 µg per HA in 0.3 mL MAS-1 (15 subjects) or HD IIV (15 subjects) followed by groups randomly assigned to receive 9 µg per HA in 0.5 mL MAS-1 (10 subjects) or HD IIV (5 subjects). Injection site tenderness, induration, and pain, and headache, myalgia, malaise and fatigue were common, resolving before day 14 post-vaccination. Clinically significant late-onset injection site reactions occurred in four of ten subjects at the 0.5 mL adjuvant dose. Safety laboratory measures were within acceptable limits. MAS-1-adjuvanted IIV enhanced mean antibody titers, mean-fold increases in antibody titer, and seroconversion rates against vaccine strains for at least 168 days post-vaccination and enhanced cross-reactive antibodies against some non-study vaccine influenza viruses.
Conclusion: MAS-1 adjuvant provided HA dose-sparing without safety concerns at the 0.3 mL dose, but the 0.5 mL dose caused late injection site reactions. MAS-1-adjuvanted IIV induced higher HAI antibody responses with prolonged durability including against historical strains, thereby providing greater potential vaccine efficacy in the elderly throughout an influenza season. Clinical Trial Registry: ClinicalTrials.gov # NCT02500680.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GJG, SEF, JM and HH report no conflicts of interest. SG and PB are employees of Mercia Pharma, Inc. in which PB has an ownership interest; HB, HM and PW are employees of Nova Immunotherapeutics; PB and PW have a financial interest in the successful development of MAS-1 as an adjuvant for clinical use. Further, PB is the inventor on a patent application relating to MAS-1 adjuvanted IIV filed in the US before the clinical studies. In addition, PB is an owner of Mercia Pharma, Inc. with a financial interest in any commercial benefit that may arise form MAS-1 adjuvanted IIV. PW is a co-owner of Mercia Pharma, Inc. and Nova Immunotherapeutics. All authors attest they meet the ICMJE criteria for authorship. All authors participated in revising the article for critically important intellectual content. GJG drafted the article and GJG and SEF supervised the acquisition of data. All authors participated in the analysis and interpretation of the data. All authors approved the final version of the article for submission.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)