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, Celsa Tajonera, Hana El Sahly, Connie Rangel, Diane Nino & 18 others Innocent Mbawuike, Tamar Blevins, Sabrina M. DiPiazza, Carol Duane, Kathleen Kohler, Michelle Mitchell, Kiana Wilder, Allison Beck, Alexis Daugherty, Mark Mulligan, Jennifer Whitaker, Nadine Rouphael, Sarah McCartney, Michelle Kroeger, Jesse LePage, Kristie Price, Ingelise Gordon, Florence Kaltovich

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0125914
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 7 2015
Externally publishedYes

Fingerprint

DNA Vaccines
randomized clinical trials
Influenza Vaccines
influenza
Randomized Controlled Trials
recombinant vaccines
vaccines
Vaccines
DNA
Human Influenza
Inactivated Vaccines
Hemagglutination
Phosphates
hemagglutination
Antigens
Vulnerable Populations
immune response
phosphates
antigens
Antibody Formation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ledgerwood, J. E., Bellamy, A. R., Belshe, R., Bernstein, D. I., Edupuganti, S., Patel, S. M., ... Kaltovich, F. (2015). DNA priming for seasonal influenza vaccine: A phase 1b double-blind randomized clinical trial. PLoS One, 10(5), [e0125914]. https://doi.org/10.1371/journal.pone.0125914

DNA priming for seasonal influenza vaccine : A phase 1b double-blind randomized clinical trial. / Ledgerwood, Julie E.; Bellamy, Abbie R.; Belshe, Robert; Bernstein, David I.; Edupuganti, Srilatha; Patel, Shital M.; Renehan, Phyllis; Zajdowicz, Thad; Schwartz, Richard; Koup, Richard; Bailer, Robert T.; Yamshchikov, Galina V.; Enama, Mary E.; Sarwar, Uzma; Larkin, Brenda; Graham, Barney S.; Tajonera, Celsa; El Sahly, Hana; Rangel, Connie; Nino, Diane; Mbawuike, Innocent; Blevins, Tamar; DiPiazza, Sabrina M.; Duane, Carol; Kohler, Kathleen; Mitchell, Michelle; Wilder, Kiana; Beck, Allison; Daugherty, Alexis; Mulligan, Mark; Whitaker, Jennifer; Rouphael, Nadine; McCartney, Sarah; Kroeger, Michelle; LePage, Jesse; Price, Kristie; Gordon, Ingelise; Kaltovich, Florence.

In: PLoS One, Vol. 10, No. 5, e0125914, 07.05.2015.

Research output: Contribution to journalArticle

Ledgerwood, JE, Bellamy, AR, Belshe, R, Bernstein, DI, Edupuganti, S, Patel, SM, Renehan, P, Zajdowicz, T, Schwartz, R, Koup, R, Bailer, RT, Yamshchikov, GV, Enama, ME, Sarwar, U, Larkin, B, Graham, BS, Tajonera, C, El Sahly, H, Rangel, C, Nino, D, Mbawuike, I, Blevins, T, DiPiazza, SM, Duane, C, Kohler, K, Mitchell, M, Wilder, K, Beck, A, Daugherty, A, Mulligan, M, Whitaker, J, Rouphael, N, McCartney, S, Kroeger, M, LePage, J, Price, K, Gordon, I & Kaltovich, F 2015, 'DNA priming for seasonal influenza vaccine: A phase 1b double-blind randomized clinical trial', PLoS One, vol. 10, no. 5, e0125914. https://doi.org/10.1371/journal.pone.0125914
Ledgerwood JE, Bellamy AR, Belshe R, Bernstein DI, Edupuganti S, Patel SM et al. DNA priming for seasonal influenza vaccine: A phase 1b double-blind randomized clinical trial. PLoS One. 2015 May 7;10(5). e0125914. https://doi.org/10.1371/journal.pone.0125914
Ledgerwood, Julie E. ; Bellamy, Abbie R. ; Belshe, Robert ; Bernstein, David I. ; Edupuganti, Srilatha ; Patel, Shital M. ; Renehan, Phyllis ; Zajdowicz, Thad ; Schwartz, Richard ; Koup, Richard ; Bailer, Robert T. ; Yamshchikov, Galina V. ; Enama, Mary E. ; Sarwar, Uzma ; Larkin, Brenda ; Graham, Barney S. ; Tajonera, Celsa ; El Sahly, Hana ; Rangel, Connie ; Nino, Diane ; Mbawuike, Innocent ; Blevins, Tamar ; DiPiazza, Sabrina M. ; Duane, Carol ; Kohler, Kathleen ; Mitchell, Michelle ; Wilder, Kiana ; Beck, Allison ; Daugherty, Alexis ; Mulligan, Mark ; Whitaker, Jennifer ; Rouphael, Nadine ; McCartney, Sarah ; Kroeger, Michelle ; LePage, Jesse ; Price, Kristie ; Gordon, Ingelise ; Kaltovich, Florence. / DNA priming for seasonal influenza vaccine : A phase 1b double-blind randomized clinical trial. In: PLoS One. 2015 ; Vol. 10, No. 5.
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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.",
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T2 - A phase 1b double-blind randomized clinical trial

AU - Ledgerwood, Julie E.

AU - Bellamy, Abbie R.

AU - Belshe, Robert

AU - Bernstein, David I.

AU - Edupuganti, Srilatha

AU - Patel, Shital M.

AU - Renehan, Phyllis

AU - Zajdowicz, Thad

AU - Schwartz, Richard

AU - Koup, Richard

AU - Bailer, Robert T.

AU - Yamshchikov, Galina V.

AU - Enama, Mary E.

AU - Sarwar, Uzma

AU - Larkin, Brenda

AU - Graham, Barney S.

AU - Tajonera, Celsa

AU - El Sahly, Hana

AU - Rangel, Connie

AU - Nino, Diane

AU - Mbawuike, Innocent

AU - Blevins, Tamar

AU - DiPiazza, Sabrina M.

AU - Duane, Carol

AU - Kohler, Kathleen

AU - Mitchell, Michelle

AU - Wilder, Kiana

AU - Beck, Allison

AU - Daugherty, Alexis

AU - Mulligan, Mark

AU - Whitaker, Jennifer

AU - Rouphael, Nadine

AU - McCartney, Sarah

AU - Kroeger, Michelle

AU - LePage, Jesse

AU - Price, Kristie

AU - Gordon, Ingelise

AU - Kaltovich, Florence

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N2 - 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.

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