A phase 1, randomized, observer blind, antigen and adjuvant dosage finding clinical trial to evaluate the safety and immunogenicity of an adjuvanted, trivalent subunit influenza vaccine in adults ≥ 65 years of age. Issue 3 (16th January 2020)

• Record Type: Journal Article
• Authors: Otten, Gillis; Matassa, Vincent; Ciarlet, Max; Leav, Brett
• Is Part Of: Vaccine. Volume 38:Issue 3(2020)
• Page Start: 578
• Page End: 587
• Publication Date: 2020-01-16
• Subjects: MF59 -- Influenza vaccine -- Elderly -- Immunogenicity -- Safety; AEs adverse events -- aTIV MF59®-adjuvanted trivalent influenza vaccine (Fluad®) -- GMR geometric mean ratio -- GMT geometric mean titre -- HA hemagglutinin -- HI hemagglutination inhibition -- MN microneutralization; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.10.058
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Highest MF59 dose had greatest influenza vaccine immunogenicity in adults ≥ 65 years. Increased immunogenicity appeared by Day 8 and persisted to Day 181. Higher local reactogenicity was observed with the highest dosage of MF59. Increasing MF59 or HA dosage did not increase unsolicited AEs. Abstract: Objective: To assess the safety and immunogenicity of the MF59®-adjuvanted trivalent influenza vaccine (aTIV; Fluad®) compared with modified aTIV formulations. Methods: A total of 196 subjects ≥ 65 years were randomized to receive 7 different formulations of vaccine containing a range of adjuvant and antigen doses by single injection, or divided into two injections at a single time point. The primary study objective was to compare the serologic response of different formulations of aTIV containing increased amounts of adjuvant and antigen 21 days after vaccination. Subjects were followed for immunogenicity and safety for one year. Results: The highest immune response, as measured by hemagglutination inhibition (HI) assay, 3 weeks after vaccination was observed in subjects in Group 6 with GMT 382.2 (95% confidence interval [CI] 237.5 to 615.0), 552.3 (364.8 to 836.1), and 54.1 (36.9 to 79.4) against A/H1N1, A/H3N2, and B respectively. Rates of seroconversion were also generally highest in this treatment group: 75% (95% CI 55.1 to 89.3), 75% (55.1 to 89.3), and 42.9% (24.5 to 62.8), respectively, against A/H1N1, A/H3N2, and B strains. The highest incidence of solicited adverse events (AEs) was reported by subjects who received both the highest dosage of antigen in combination with the highest dosage of adjuvant at the same site: 67.9% and 57.1% in Groups 4 and 6, respectively. The majority of solicited AEs were mild to moderate in severity. The number of unsolicited AEs was similar across the different dosages. Conclusion: In this phase I trial of adults ≥ 65 years of age who received increased adjuvant and antigen dosages relative to the licensed aTIV, increased dosage of MF59 resulted in increased immunogenicity against all 3 components of seasonal influenza vaccine. The increase in immunogenicity was accompanied by an increase in the incidence of local reactogenicity.