DNA Priming for Seasonal Influenza Vaccine: A Phase 1b Double-Blind Randomized Clinical Trial

• Type of Material: Article
• Authors: Julie E. Ledgerwood, National Institutes of Allergy and Infectious Diseases; Abbie R. Bellamy, The EMMES Corporation; Robert Belshe, Saint Louis University; David I. Bernstein, University of Cincinnati; Srilatha Edupuganti, Emory University; Shital M. Patel, Baylor College of Medicine; Phyllis Renehan, The EMMES Corporation; Thad Zajdowicz, The EMMES Corporation; Richard Schwartz, National Institutes of Allergy and Infectious Diseases; Richard Koup, National Institutes of Allergy and Infectious Diseases; Robert T. Bailer, National Institutes of Allergy and Infectious Diseases; Galina V. Yamshchikov, National Institutes of Allergy and Infectious Diseases; Mary E. Enama, National Institutes of Allergy and Infectious Diseases; Uzma Sarwar, National Institutes of Allergy and Infectious Diseases; Brenda Larkin, National Institutes of Allergy and Infectious Diseases; Barney S. Graham, National Institutes of Allergy and Infectious Diseases; Nadine Rouphael, Emory University
• Language: English
• Date: 2015-05-07
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2015, Public Library of Science. All rights reserved.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0125914
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 10
• Issue: 5
• Start Page: e0125914
• End Page: e0125914
• Grant/Funding Information: The EMMES Corporation provided support in the form of salaries for authors AB, PR and TZ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The specific roles of these authors are articulated in the ‘author contributions’ section.; This clinical study was conducted with funding and support by the National Institute of Allergy and Infectious Diseases (NIAID) Intramural Research program, using resources provided by the American Recovery and Reinvestment Act of 2009 (Recovery Act), and contract #HHSN272201000049I awarded to the EMMES Corporation (AB, TZ, PR, RB, RTB, DB, SE, SP).
• Keywords: Science & Technology - Other Topics; Multidisciplinary Sciences; Science & Technology; INTERVAL
• Research Categories: Health Sciences, Public Health; Health Sciences, Epidemiology

Abstract

Background The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost. Methods Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective. Results The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study. Conclusion While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative.