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-Reference-Cited by-同舟云学术

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

Published:2024-03-27 Issue:6 Volume:78 Page:1757-1768
ISSN:1058-4838
Container-title:Clinical Infectious Diseases
language:en
Short-container-title:

Author:

Rostad Christina A¹²^ORCID,Atmar Robert L³,Walter Emmanuel B⁴,Frey Sharon⁵,Meier Jeffery L⁶,Sherman Amy C⁷,Lai Lilin⁷,Tsong Rachel⁸,Kao Carol M¹²,Raabe Vanessa⁷⁹,El Sahly Hana M³,Keitel Wendy A³,Whitaker Jennifer A³,Smith Michael J⁴,Schmader Kenneth E¹⁰,Swamy Geeta K¹¹,Abate Getahun⁵,Winokur Patricia⁶,Buchanan Wendy¹²,Cross Kaitlyn⁸,Wegel Ashley⁸,Xu Yongxian⁷,Yildirim Inci¹²,Kamidani Satoshi¹²,Rouphael Nadine⁷,Roberts Paul C¹²,Mulligan Mark J⁷⁹,Anderson Evan J¹²⁷

Affiliation:

1. Department of Pediatrics, Emory University School of Medicine , Atlanta, Georgia , USA

2. Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta , Atlanta, Georgia , USA

3. Departments of Medicine and Molecular Virology & Microbiology, Baylor College of Medicine , Houston, Texas , USA

4. Department of Pediatrics and Duke Human Vaccine Institute, Duke University , Durham, North Carolina , USA

5. Center for Vaccine Development, Saint Louis University , St. Louis, Missouri , USA

6. Department of Internal Medicine, University of Iowa , Iowa City, Iowa , USA

7. Hope Clinic, Department of Medicine, Emory University School of Medicine , Atlanta, Georgia , USA

8. Emmes, Inc. , Rockville, Maryland , USA

9. New York University Langone Vaccine Center, NYU Grossman School of Medicine , New York, New York , USA

10. Department of Medicine-Geriatrics, Duke University and GRECC, Durham VA Health Care System , Durham, North Carolina , USA

11. Department of Obstetrics and Gynecology and Duke Human Vaccine Institute, Duke University , Durham, North Carolina , USA

12. Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Rockville, Maryland , USA

Abstract

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.

Funder

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Emory

Baylor College of Medicine

University of Iowa and National Center for Advancing Translational Sciences

University of Iowa

Saint Louis University

Duke University

Georgia Research Alliance

Emory University School of Medicine

Children’s Healthcare of Atlanta