@article{3973786bc1b74b5e9311c4376e859b30,
title = "Immunogenicity and safety of different dose schedules and antigen doses of an MF59-adjuvanted H7N9 vaccine in healthy adults aged 65 years and older",
abstract = "Background: The number of human influenza A (H7N9) infections has escalated since 2013 with high resultant mortality. We conducted a phase II, randomized, partially-blinded trial to evaluate the safety and immunogenicity of an MF59-adjuvanted inactivated, split virion, H7N9 influenza vaccine (H7N9 IIV) administered at various dose levels and schedules in older adults. Methods: 479 adults ≥ 65 years of age in stable health were randomized to one of six groups to receive either 3.75, 7.5 or 15 µg of influenza A/Shanghai/02/2013 (H7N9) IIV adjuvanted with MF59 given as a 3-dose series either on days 1, 28 and 168 or on days 1, 57 and 168. Immunogenicity was assessed using both hemagglutination inhibition (HAI) and microneutralization (MN) assays prior to and 28 days following each dose. Safety was assessed through 1 year following the last dose. Results: Subjects in all groups had only modest immune responses, with the HAI GMT < 20 after the second vaccine dose and <29 after the third vaccine dose. HAI titers ≥ 40 were seen in <37% of subjects after the second dose and <49% after the third dose. There were no significant differences seen between the two dose schedules. MN titers followed similar patterns, although the titers were approximately two-fold higher than the HAI titers. Logistic regression modeling demonstrated no statistically significant associations between the immune responses and age, sex or body mass index whereas recent prior receipt of seasonal influenza vaccine significantly reduced the HAI response [OR 0.13 (95% CI 0.05, 0.33); p < 0.001]. Overall, the vaccine was well tolerated. Two mild potentially immune mediated adverse events occurred, lichen planus and guttate psoriasis. Conclusions: MF59-adjuvanted H7N9 IIV was only modestly immunogenic in the older adult population following three doses. There were no significant differences in antibody responses noted among the various antigen doses or the two dose schedules.",
keywords = "Avian influenza, H7N9, MF59, influenza vaccine",
author = "{the DMID 13-0034 H7N9 Vaccine Study Group} and Patricia Winokur and {El Sahly}, {Hana M.} and Mulligan, {Mark J.} and Frey, {Sharon E.} and Richard Rupp and Anderson, {Evan J.} and Edwards, {Kathryn M.} and Bernstein, {David I.} and Kenneth Schmader and Jackson, {Lisa A.} and Chen, {Wilbur H.} and Heather Hill and Abigail Bellamy",
note = "Funding Information: We are grateful to the 13-0034 Study Team Group who participated in the implementation of this study including Jack Stapleton, Dilek Ince from the University of Iowa; Nadine Rouphael, Jumi Yi, Andres Camacho-Gonzalez, Inci Yildirim and Larry Anderson from Emory University, Irene Graham and Edwin Anderson from Saint Louis University, Rebecca Brady from Cincinnati Children's Hospital Medical Center, Clarence Buddy Creech at Vanderbilt University, Robert Atmar, Wendy Keitel and Shital Patel from Baylor College of Medicine, and Ashley Wegel and Karineh Tarpinian from Emmes. Additionally, we thank the Vaccine Treatment and Evaluation Unit study teams at each institution and the exceptional contributions provided by the scientific and professional staff from the National Institutes of Health, Division of Microbiology and Infectious Diseases. We are grateful for the manuscript review expertise provided by the following colleagues at BARDA: Corrina Pavetto, MS, Bai Yeh, MBA, Vittoria Cioce, PhD, Christine Oshansky, PhD, and James King, MD. These individuals were not specifically compensated for these contributions. Funding Information: This work was funded by the National Institutes of Health, National Institute of Allergy and Infectious Diseases Contract Numbers Vaccine and Treatment Evaluation Unit Contracts HHSN2722013000201 (University of Iowa), HHSN27220080000C (Vanderbilt University), HHSN272200800006C (Cincinnati Children{\textquoteright}s Hospital), HHSN272200800005C (Emory University), HHSN272201300019I (Kaiser), HHHSN272201300018I (Emory University), HHSN272200800002C and HHSN272201300015I (Baylor College of Medicine), Emory University (HHSN272200800005C, HHSN272200800001C (University of Maryland), HHSN272200800003C (Saint Louis University), 272,201,300,171 (Duke University), HHSN272200800013C and HHSN272201500002C (Emmes), and the Institute for Clinical and Translational Science at the University of Iowa (UL1TR002537) and the Clinical and Translational Science Award funds from NCATS at Vanderbilt University (2UL1TR000445), and the Atlanta Clinical and Translational Science Award from NCATS (UL1TR000454). The 2013 H7N9 vaccine and MF59 adjuvant were provided by the US Department of Health and Human Services (HHS) Biomedical Advanced Research and Development Authority (BARDA) from the National Prepandemic Influenza Vaccine Stockpile and were manufactured by Sanofi Pasteur and Seqirus, respectively. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2021",
month = feb,
day = "22",
doi = "10.1016/j.vaccine.2020.11.051",
language = "English (US)",
volume = "39",
pages = "1339--1348",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "8",
}