SEATTLE—People were first reported infected with the avian influenza A H7N9 (bird flu) virus in China in 2013, and hundreds of cases have been documented since then. Most have probably resulted from exposure to infected poultry, not to other people. But experts are preparing for the potential for the virus to change to facilitate spread from person to person.
As part of that effort, the national Vaccine and Treatment Evaluation Unit (VTEU) network is reporting that two adjuvants increased the body’s immune responses to two doses of an inactivated influenza A H7N9 virus in a phase 2 trial including nearly 1,000 adults, age 19 to 64. The July 21 Journal of the American Medical Association published it: “Effect of varying doses of a monovalent H7N9 influenza vaccine with and without AS03 and MF59 adjuvants on immune response: A randomized clinical trial.”
Adjuvants are substances that may be added to vaccines to enhance the immune response by producing more antibodies and longer-lasting protection, explained lead author Lisa A. Jackson, MD, MPH, a senior investigator at Group Health Research Institute (GHRI). This makes the vaccine more effective and can minimize how much of it needs to be injected. Previous research had shown that inactivated influenza A H7N7 vaccine would need an adjuvant for an adequate immune response. The current study is the first head-to-head comparison of these two squalene-based adjuvants: AS03 and MF59.
“Our findings can inform influenza pandemic preparedness programs,” Dr. Jackson said. “We concluded that AS03 should be considered a first-line adjuvant for strategies incorporating an inactivated H7N9 vaccine in adults.”
In the study, conducted at five VTEU sites including Group Health, most participants required two doses of the vaccine to produce a detectable amount of antibodies. The response was lowest with no adjuvant, highest with AS03, and in between with MF59.
Most prior research has evaluated vaccines and adjuvants produced by a single manufacturer, often combining them before release. “By contrast, our study reflected more real-world conditions, in which adjuvants are used from the stockpile and mixed with vaccine at the point of use, likely combining adjuvants produced by different manufacturers,” Dr. Jackson said. “We found that on-site mixing of vaccine with adjuvants from other manufacturers produced formulations that people tolerated well and that augmented the immune response to the vaccine.”
Dr. Jackson’s coauthors are James D. Campbell, MD, MS, Karen L. Kotloff, MD, and Andrea A. Berry, MD, of the University of Maryland School of Medicine, in Baltimore; Sharon E. Frey, MD, Irene Graham, MD, and Edwin L. Anderson, MD, of Saint Louis University School of Medicine; Kathryn M. Edwards, MD, C. Buddy Creech, MD, MPH, and Isaac P. Thomsen, MD, of Vanderbilt University Medical Center, in Nashville; Wendy A. Keitel, MD, Robert L Atmar, MD, Shital M. Patel, MD, Andres F. Gutierrez, MD, and Hana M. El Sahly, MD, of Baylor College of Medicine, in Houston; Heather Hill, MS, and Abbie R. Bellamy, PhD, of The EMMES Corporation, in Rockville, Md.; and Diana L. Noah, PhD, of the Southern Research Institute, in Birmingham, Ala.
Federal funds from the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the U.S. Department of Health and Human Services supported this work under contracts HHSN272200800004C (Group Health), HHSN27220080000C (Vanderbilt University), HHSN272200800001C (University of Maryland), HHSN272200800002C (Baylor College of Medicine), HHSN272200800003C (Saint Louis University), HHSN2722012000031 and HHSN27200003 (Battelle and subcontractor Southern Research, Inc.), and HHSN272200800013C (EMMES Corporation). At the University of Maryland, additional funding sources, including the University of Maryland General Clinical Research Center grant M01-RR-016500 from the NCRR, and by NCRR grant K12-RR-023250 also provided partial support. The U.S. Department of Health and Human Services Biomedical Advanced Research and Development Authority from the National Pre-pandemic Influenza Vaccine Stockpile provided the vaccine and adjuvants, which were manufactured by Sanofi Pasteur (H7N9 vaccine), Novartis Vaccines (MF59 adjuvant), and GlaxoSmithKline (AS03 adjuvant).
Trial registration: clinicaltrials.gov identifier: NCT01942265
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NEJM Catalyst, Apr. 11, 2018