Phase 1 study of pandemic H1 DNA vaccine in healthy adults

Michelle C. Crank, Ingelise J. Gordon, Galina V. Yamshchikov, Sandra Sitar, Zonghui Hu, Mary E. Enama, LaSonji A. Holman, Robert T. Bailer, Melissa B. Pearce, Richard A. Koup, John R. Mascola, Gary J. Nabel, Terrence M. Tumpey, Richard M. Schwartz, Barney S. Graham, Julie E. Ledgerwood, Sarah Plummer, Cynthia Starr Hendel, Laura Novik, Pamela CostnerKathy Zephir, Floreliz Mendoza, Jamie Saunders, Nina Berkowitz, Brandon Wilson, Brenda Larkin, Joseph Casazza, Uzma N. Sarwar, Judy Stein, Olga Vasilenko, Hope Decederfelt, Judith Starling, Phyllis Renehan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). Methods 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. Results Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. Conclusions H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.

Original languageEnglish (US)
Article numbere0123969
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 17 2015
Externally publishedYes

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Inactivated Vaccines
DNA Vaccines
inactivated vaccines
Pandemics
pandemic
recombinant vaccines
T-cells
DNA
influenza
T-lymphocytes
vaccination
H1N1 Subtype Influenza A Virus
neutralization tests
Vaccination
Viruses
T-Lymphocytes
Assays
Antibody Formation
immune response
Clinical laboratories

ASJC Scopus subject areas

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

Cite this

Crank, M. C., Gordon, I. J., Yamshchikov, G. V., Sitar, S., Hu, Z., Enama, M. E., ... Renehan, P. (2015). Phase 1 study of pandemic H1 DNA vaccine in healthy adults. PLoS One, 10(4), [e0123969]. https://doi.org/10.1371/journal.pone.0123969

Phase 1 study of pandemic H1 DNA vaccine in healthy adults. / Crank, Michelle C.; Gordon, Ingelise J.; Yamshchikov, Galina V.; Sitar, Sandra; Hu, Zonghui; Enama, Mary E.; Holman, LaSonji A.; Bailer, Robert T.; Pearce, Melissa B.; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.; Tumpey, Terrence M.; Schwartz, Richard M.; Graham, Barney S.; Ledgerwood, Julie E.; Plummer, Sarah; Hendel, Cynthia Starr; Novik, Laura; Costner, Pamela; Zephir, Kathy; Mendoza, Floreliz; Saunders, Jamie; Berkowitz, Nina; Wilson, Brandon; Larkin, Brenda; Casazza, Joseph; Sarwar, Uzma N.; Stein, Judy; Vasilenko, Olga; Decederfelt, Hope; Starling, Judith; Renehan, Phyllis.

In: PLoS One, Vol. 10, No. 4, e0123969, 17.04.2015.

Research output: Contribution to journalArticle

Crank, MC, Gordon, IJ, Yamshchikov, GV, Sitar, S, Hu, Z, Enama, ME, Holman, LA, Bailer, RT, Pearce, MB, Koup, RA, Mascola, JR, Nabel, GJ, Tumpey, TM, Schwartz, RM, Graham, BS, Ledgerwood, JE, Plummer, S, Hendel, CS, Novik, L, Costner, P, Zephir, K, Mendoza, F, Saunders, J, Berkowitz, N, Wilson, B, Larkin, B, Casazza, J, Sarwar, UN, Stein, J, Vasilenko, O, Decederfelt, H, Starling, J & Renehan, P 2015, 'Phase 1 study of pandemic H1 DNA vaccine in healthy adults', PLoS One, vol. 10, no. 4, e0123969. https://doi.org/10.1371/journal.pone.0123969
Crank MC, Gordon IJ, Yamshchikov GV, Sitar S, Hu Z, Enama ME et al. Phase 1 study of pandemic H1 DNA vaccine in healthy adults. PLoS One. 2015 Apr 17;10(4). e0123969. https://doi.org/10.1371/journal.pone.0123969
Crank, Michelle C. ; Gordon, Ingelise J. ; Yamshchikov, Galina V. ; Sitar, Sandra ; Hu, Zonghui ; Enama, Mary E. ; Holman, LaSonji A. ; Bailer, Robert T. ; Pearce, Melissa B. ; Koup, Richard A. ; Mascola, John R. ; Nabel, Gary J. ; Tumpey, Terrence M. ; Schwartz, Richard M. ; Graham, Barney S. ; Ledgerwood, Julie E. ; Plummer, Sarah ; Hendel, Cynthia Starr ; Novik, Laura ; Costner, Pamela ; Zephir, Kathy ; Mendoza, Floreliz ; Saunders, Jamie ; Berkowitz, Nina ; Wilson, Brandon ; Larkin, Brenda ; Casazza, Joseph ; Sarwar, Uzma N. ; Stein, Judy ; Vasilenko, Olga ; Decederfelt, Hope ; Starling, Judith ; Renehan, Phyllis. / Phase 1 study of pandemic H1 DNA vaccine in healthy adults. In: PLoS One. 2015 ; Vol. 10, No. 4.
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abstract = "Background A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). Methods 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. Results Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. Conclusions H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.",
author = "Crank, {Michelle C.} and Gordon, {Ingelise J.} and Yamshchikov, {Galina V.} and Sandra Sitar and Zonghui Hu and Enama, {Mary E.} and Holman, {LaSonji A.} and Bailer, {Robert T.} and Pearce, {Melissa B.} and Koup, {Richard A.} and Mascola, {John R.} and Nabel, {Gary J.} and Tumpey, {Terrence M.} and Schwartz, {Richard M.} and Graham, {Barney S.} and Ledgerwood, {Julie E.} and Sarah Plummer and Hendel, {Cynthia Starr} and Laura Novik and Pamela Costner and Kathy Zephir and Floreliz Mendoza and Jamie Saunders and Nina Berkowitz and Brandon Wilson and Brenda Larkin and Joseph Casazza and Sarwar, {Uzma N.} and Judy Stein and Olga Vasilenko and Hope Decederfelt and Judith Starling and Phyllis Renehan",
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T1 - Phase 1 study of pandemic H1 DNA vaccine in healthy adults

AU - Crank, Michelle C.

AU - Gordon, Ingelise J.

AU - Yamshchikov, Galina V.

AU - Sitar, Sandra

AU - Hu, Zonghui

AU - Enama, Mary E.

AU - Holman, LaSonji A.

AU - Bailer, Robert T.

AU - Pearce, Melissa B.

AU - Koup, Richard A.

AU - Mascola, John R.

AU - Nabel, Gary J.

AU - Tumpey, Terrence M.

AU - Schwartz, Richard M.

AU - Graham, Barney S.

AU - Ledgerwood, Julie E.

AU - Plummer, Sarah

AU - Hendel, Cynthia Starr

AU - Novik, Laura

AU - Costner, Pamela

AU - Zephir, Kathy

AU - Mendoza, Floreliz

AU - Saunders, Jamie

AU - Berkowitz, Nina

AU - Wilson, Brandon

AU - Larkin, Brenda

AU - Casazza, Joseph

AU - Sarwar, Uzma N.

AU - Stein, Judy

AU - Vasilenko, Olga

AU - Decederfelt, Hope

AU - Starling, Judith

AU - Renehan, Phyllis

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N2 - Background A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). Methods 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. Results Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. Conclusions H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.

AB - Background A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). Methods 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. Results Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. Conclusions H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.

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