A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults

Authors

Christina A Rostad
Robert L Atmar
Emmanuel B Walter
Sharon Frey
Jeffery L Meier
Amy C Sherman
Lilin Lai
Rachel Tsong
Carol M Kao
Vanessa Raabe
Hana M El Sahly
Wendy A Keitel
Jennifer A Whitaker
Michael J Smith
Kenneth E Schmader
Geeta K Swamy
Getahun Abate
Patricia Winokur
Wendy Buchanan
Kaitlyn Cross
Ashley Wegel
Yongxian Xu
Inci Yildirim
Satoshi Kamidani
Nadine Rouphael
Paul C Roberts
Mark J Mulligan
Evan J Anderson

Publication Date

6-14-2024

Journal

Clinical Infectious Disease

DOI

10.1093/cid/ciae173

PMID

38537255

PMCID

PMC11175706

PubMedCentral® Posted Date

3-27-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Influenza Vaccines, Adult, Male, Female, Middle Aged, Influenza A Virus, H7N9 Subtype, Vaccines, Inactivated, Antibodies, Viral, Influenza, Human, Young Adult, Immunization, Secondary, Immunization Schedule, Hemagglutination Inhibition Tests, United States, Immunogenicity, Vaccine, Antibodies, Neutralizing, Polysorbates, alpha-Tocopherol, Squalene, Healthy Volunteers, Drug Combinations, Adjuvants, Vaccine, Vaccination, Adjuvants, Immunologic, avian influenza, boost, antibody, 2013 H7N9, 2017 H7N9

Abstract

Introduction: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs.

Methods: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed.

Results: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval.

Conclusions: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807.