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

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

doi:10.1093/cid/ciae173

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

Clin Infect Dis. 2024 Mar 27:ciae173. doi: 10.1093/cid/ciae173. Online ahead of print.

Authors

Christina A Rostad^{1

2}, Robert L Atmar³, Emmanuel B Walter⁴, Sharon Frey⁵, Jeffery L Meier⁶, Amy C Sherman⁷, Lilin Lai⁷, Rachel Tsong⁸, Carol M Kao^{1

2}, Vanessa Raabe^{7

9}, Hana M El Sahly³, Wendy A Keitel³, Jennifer A Whitaker³, Michael J Smith⁴, Kenneth E Schmader¹⁰, Geeta K Swamy¹¹, Getahun Abate⁵, Patricia Winokur⁶, Wendy Buchanan¹², Kaitlyn Cross⁸, Ashley Wegel⁸, Yongxian Xu⁷, Inci Yildirim^{1

2}, Satoshi Kamidani^{1

2}, Nadine Rouphael⁷, Paul C Roberts¹², Mark J Mulligan^{7

9}, Evan J Anderson^{1

2

7}

Affiliations

¹ Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
² Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Atlanta, GA, USA.
³ Departments of Medicine and Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, USA.
⁴ Department of Pediatrics and Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
⁵ Center for Vaccine Development, Saint Louis University, St. Louis, MO, USA.
⁶ Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
⁷ Hope Clinic, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
⁸ Emmes, Inc. Rockville, MD, USA.
⁹ New York University Langone Vaccine Center, NYU Grossman School of Medicine, New York, NY, USA.
¹⁰ Department of Medicine-Geriatrics, Duke University and GRECC, Durham VA Health Care System Durham, NC, USA.
¹¹ Department of Obstetrics and Gynecology and Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
¹² Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.

PMID: 38537255
DOI: 10.1093/cid/ciae173

Abstract

Introduction: A surge of human influenza A(H7N9) cases began in 2016 in China due to 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, multi-center Phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with two different boost intervals (21 versus 120 days) and two dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition (HAI) 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 HAI GMT (95%CI) observed against the 2017 A(H7N9) strain was 133.4 (83.6, 212.6) among participants who received homologous, adjuvanted 3.75 ug+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. (NCT03589807).

Keywords: 2013 H7N9; 2017 H7N9; Avian Influenza; antibody; boost.

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Associated data

ClinicalTrials.gov/NCT03589807