160. Safety and Immunogenicity of Escalating Dose Formulations of High-dose Quadrivalent Influenza Vaccine in Children 6 Months Through < 18 Years of Age

BACKGROUND: Children do not respond immunologically as well as adults to standard-dose (SD) influenza vaccination and remain at increased risk of influenza and its complications. A method to improve efficacy in children may be to increase antigen amount per dose, a successful strategy used in older adults. Trivalent high-dose (HD) influenza vaccine (60ug hemagglutinin/strain) showed significantly improved effectiveness for prevention of clinical outcomes related to influenza in adults ≥65 years; moreover, a quadrivalent HD formulation was approved by US FDA (2019) for use in this group. METHODS: A Phase 2, randomized, modified double blind study (NCT03698279) was conducted in US and Canadian children to evaluate safety and immunogenicity of IIV4-HD compared to an IIV4-SD and adjuvanted trivalent influenza vaccine (aIIV3). Children (n=661, 6 months through < 18 years) were assigned to receive intramuscularly 1 of 3 formulations of IIV4-HD (30, 45, or 60 µg HA/strain/dose), a licensed IIV4-SD, or a licensed aIIV3. Depending on child’s previous influenza vaccination status and age, they received 1 or 2 doses of study vaccine 28 days apart. Post-vaccination (28 days after each vaccination) geometric mean titers (GMTs) and seroconversion rates were measured using hemagglutinin inhibition (HAI) assay. Reactogenicity data were collected through 1 week; safety data were collected through 6 months post-vaccination. RESULTS: IIV4-HD was more reactogenic than IIV4-SD, but unsolicited related adverse events were similar (Table 1). No related serious adverse events or deaths occurred. A dose-related increase in HAI GMT ratio was observed across the age range for A/H3N2 but only in children 6 months through < 3 years for A/H1N1 and the 2 B strains (Table 2). Compared with IIV4-SD, the 60 µg HA/strain/dose formulation of IIV4-HD generated highest HAI GMT ratios and high seroconversion rates for all 4 strains in US children 6 months through < 3 years. Canadian children receiving IIV4-HD generated HAI titers incongruent to those of US children receiving IIV4-HD, limiting direct comparison against aIIV3. Safety Overview (US and Canadian subjects 6 months through <18 years) [Image: see text] HAI GMT Ratios (QIV-HD/QIV-SD) at 28 days After the Last Vaccination (US subjects 6 months through <18 years) [Image: see text] CONCLUSION: The favorable safety profile and the HAI GMT ratios support pediatric dose selection of 60µg HA/strain/dose as most appropriate to evaluate in Phase 3. DISCLOSURES: Leejah Chang, MD, Sanofi Pasteur (Employee) Evan J. Anderson, MD, Sanofi Pasteur (Scientific Research Study Investigator) Robert Jeanfreau, MD, Sanofi Pasteur (Scientific Research Study Investigator) Ying He, PhD, Otsuka Pharmaceutical (Employee)Sanofi Pasteur (Other Financial or Material Support, Former employee) Bryony Hicks, BSc, Sanofi Pasteur (Employee) Anju Shrestha, MD, Sanofi Pasteur (Employee) Aseem Pandey, PhD, Sanofi Pasteur (Employee)Sanofi Pasteur (Employee) Rawia Khoury, BSc, Sanofi Pasteur (Employee) Iris De Bruijn, PhD, Sanofi Pasteur (Employee) Victoria Landolfi, MS, MBA, Sanofi Pasteur (Employee)