Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults

Abstract

BackgroundA 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).Methods20 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.ResultsVaccinations 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.ConclusionsH1 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.Trial RegistrationClinicaltrials.gov NCT00973895

Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost

“…As we demonstrated in our studies with H1N1 pandemic influenza, HA DNA vaccines can be produced faster than inactivated vaccine, and there is a real potential to vaccinate with the HA DNA prime before inactivated vaccine is available in the season [12]. …”

“…Compared to other vaccine technologies, rapid production of DNA vaccines that encode for particular antigens is relatively easy [7–12]. Priming with DNA vaccines is an approach studied by VRC/NIAID/NIH as a preventive vaccination strategy against multiple pathogens [9,13] as well as by others for different pathogens and cancer [14–17].…”

Influenza nucleoprotein DNA vaccination by a skin targeted, dry coated, densely packed microprojection array (Nanopatch) induces potent antibody and CD8 + T cell responses

“…DNA vaccines are inexpensive, easy and faster to produce than protein vaccines [1]. They are stable at room temperature, and could induce strong long lasting humoral and cellular immune responses that confer protection against the disease [2].…”

Receptor-binding domain of MERS-CoV with optimal immunogen dosage and immunization interval protects human transgenic mice from MERS-CoV infection

“…Instead of utilizing 3 doses of immunizations, 26,29 our findings revealed that a satisfactory neutralizing antibody response could be achieved for a regimen consisting of 2 doses of MERS-CoV RBD protein at a 4-week interval, similar to the typical regimen of clinically trialed vaccines against other viral diseases. 46,47 These neutralizing antibodies were able to keep at similar, or higher, levels after 40 days post-last immunization to potently neutralize infections from MERS pseudovirus and live MERS-CoV (Table 1). Importantly, the reduction of immunogen doses and extension of vaccination interval have afforded MERS-CoV RBD protein the ability to induce suitable neutralizing antibodies that were maintained for at least 4 months during the detection period to protect aged hDPP4-Tg mice against lethal MERS-CoV infection.…”