tetano
Editor, Senior Moderator
PLoS One. 2015 Apr 17;10(4):e0123969. doi: 10.1371/journal.pone.0123969. eCollection 2015.
[h=1]Phase 1 study of pandemic h1 DNA vaccine in healthy adults.[/h] Crank MC[SUP]1[/SUP], Gordon IJ[SUP]1[/SUP], Yamshchikov GV[SUP]1[/SUP], Sitar S[SUP]1[/SUP], Hu Z[SUP]2[/SUP], Enama ME[SUP]1[/SUP], Holman LA[SUP]1[/SUP], Bailer RT[SUP]1[/SUP], Pearce MB[SUP]3[/SUP], Koup RA[SUP]1[/SUP], Mascola JR[SUP]1[/SUP], Nabel GJ[SUP]1[/SUP], Tumpey TM[SUP]3[/SUP], Schwartz RM[SUP]1[/SUP], Graham BS[SUP]1[/SUP], Ledgerwood JE[SUP]1[/SUP]; VRC 308 Study Team.
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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).
[h=4]METHODS:[/h] 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] 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.
[h=4]TRIAL REGISTRATION:[/h] Clinicaltrials.gov NCT00973895.
PMID: 25884189 [PubMed - in process]
[h=1]Phase 1 study of pandemic h1 DNA vaccine in healthy adults.[/h] Crank MC[SUP]1[/SUP], Gordon IJ[SUP]1[/SUP], Yamshchikov GV[SUP]1[/SUP], Sitar S[SUP]1[/SUP], Hu Z[SUP]2[/SUP], Enama ME[SUP]1[/SUP], Holman LA[SUP]1[/SUP], Bailer RT[SUP]1[/SUP], Pearce MB[SUP]3[/SUP], Koup RA[SUP]1[/SUP], Mascola JR[SUP]1[/SUP], Nabel GJ[SUP]1[/SUP], Tumpey TM[SUP]3[/SUP], Schwartz RM[SUP]1[/SUP], Graham BS[SUP]1[/SUP], Ledgerwood JE[SUP]1[/SUP]; VRC 308 Study Team.
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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).
[h=4]METHODS:[/h] 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] 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.
[h=4]TRIAL REGISTRATION:[/h] Clinicaltrials.gov NCT00973895.
PMID: 25884189 [PubMed - in process]