Immunogenicity.

<p>(A) Hemagglutination Inhibition (HAI) assay with A/Mexico/4482/2009 H1N1 virus (B) Neutralizing antibodies were evaluated by the capacity of sera to prevent infection of 293A cells by replication-incompetent H1-pseudotyped virus. The 80% inhibition serum titers are shown. (C) End-point ELISA titers of H1 A/California/04/2009(H1N1) specific antibodies are shown. Pre-vaccination titers have been subtracted from each plotted value. (D) H1-specific T cell responses are shown as a number of spot forming cells (SFC) per 10⁶ PBMC as measured by ELISpot assay. Geometric means and 95% CI are shown for the study groups.</p

Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults

<div><p>Background</p><p>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).</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p><p>Trial Registration</p><p>Clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00973895" target="_blank">NCT00973895</a></p></div

Rapid DNA Vaccine Manufacturing in Response to Influenza Pandemic.

<p>Rapid DNA Vaccine Manufacturing in Response to Influenza Pandemic.</p

Consort Flow Diagram.

<p>Number of individuals assessed for eligibility, enrolled and followed up.</p

Frequency of Adverse Events.

<p>Solicited reactogenicity was collected for 7 days after each vaccination for 21 days total after H1 DNA administered 3 times, and for 7 days after MIV administration. Each vaccine recipient is counted once at worst severity for any local and systemic parameter.</p><p>Frequency of Adverse Events.</p

Baseline Characteristics of Participants.

<p>Baseline Characteristics of Participants.</p