DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized clinical trial
Julie E Ledgerwood, Abbie R Bellamy, Robert Belshe, David I Bernstein, Srilatha Edupuganti, Shital M Patel, Phyllis Renehan, Thad Zajdowicz, Richard Schwartz, Richard Koup, Robert T Bailer, Galina V Yamshchikov, Mary E Enama, Uzma Sarwar, Brenda Larkin, Barney S Graham, VRC 701 study team, Celsa Tajonera, Hana El Sahly, Connie Rangel, Diane Nino, Innocent Mbawuike, Tamar Blevins, Sabrina M DiPiazza, Carol Duane, Kathleen Kohler, Michelle Mitchell, Karla Mosby, Kiana Wilder, Allison Beck, Alexis Daugherty, Mark Mulligan, Jennifer Whitaker, Nadine Rouphael, Sarah McCartney, Michelle Kroeger, Jesse LePage, Kristie Price, Ingelise Gordon, Florence Kaltovich, Julie E Ledgerwood, Abbie R Bellamy, Robert Belshe, David I Bernstein, Srilatha Edupuganti, Shital M Patel, Phyllis Renehan, Thad Zajdowicz, Richard Schwartz, Richard Koup, Robert T Bailer, Galina V Yamshchikov, Mary E Enama, Uzma Sarwar, Brenda Larkin, Barney S Graham, VRC 701 study team, Celsa Tajonera, Hana El Sahly, Connie Rangel, Diane Nino, Innocent Mbawuike, Tamar Blevins, Sabrina M DiPiazza, Carol Duane, Kathleen Kohler, Michelle Mitchell, Karla Mosby, Kiana Wilder, Allison Beck, Alexis Daugherty, Mark Mulligan, Jennifer Whitaker, Nadine Rouphael, Sarah McCartney, Michelle Kroeger, Jesse LePage, Kristie Price, Ingelise Gordon, Florence Kaltovich
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.
Trial registration: ClinicalTrials.gov NCT01498718.
Conflict of interest statement
Competing Interests: 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). AB, TZ, PR are salaried employees of the EMMES Corporation. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
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Source: PubMed