ABSTRACT
A phase I clinical trial was conducted to evaluate a monovalent influenza DNA vaccine containing the HA gene from A/Panama/2007/99 delivered by particle-mediated epidermal delivery (PMED). Three groups of 12 healthy adult subjects received a single dose on day 0 of either 1, 2 or 4 microg of DNA vaccine, delivered as 1, 2 or 4 PMED administrations. The PMED influenza DNA vaccine elicited serum hemagglutination-inhibition (HAI) antibody responses at all three dose levels, with the highest and most consistent responses in subjects vaccinated with the highest dose level. Antibody responses were greatest at the last time point tested, day 56. Treatment-related reactions were mild to moderate, and included skin reactions at the vaccine site. These results provide a preliminary indication of the safety and immunogenicity of a prototype epidermal DNA vaccine for influenza.
Subject(s)
Epidermis , Influenza A virus/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Vaccines, DNA/immunology , Adult , Antibodies, Viral/biosynthesis , Dose-Response Relationship, Immunologic , Female , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Influenza, Human/immunology , Male , Vaccines, DNA/administration & dosage , Vaccines, DNA/adverse effectsABSTRACT
This clinical delivery system bridging study evaluated the performance of a single-use disposable, commercial prototype device (designated ND 5.5) for particle-mediated epidermal delivery (PMED) of a nucleic acid vaccine against Hepatitis B virus (HBV). Healthy adults, previously immunized with licensed HBV vaccine, received a single boost vaccination of HBV nucleic acid vaccine administered by ND 5.5 or XR-1, the clinical research device used in previous clinical trials. Similar increases in anti-HBV surface antigen serum antibody titers and cell-mediated immune responses were produced by ND 5.5 and XR-1 when delivering comparable effective doses of the vaccine. The overall intensity of the immune response was lower in those subjects vaccinated with two, rather than 4 administrations of vaccine delivered by ND 5.5. Skin reactions at sites of vaccine administration were equivalent with both devices. This is the first clinical demonstration of the safe and effective PMED of a nucleic acid vaccine with the ND 5.5 device.
Subject(s)
Hepatitis B Vaccines/administration & dosage , Hepatitis B/prevention & control , Injections, Jet/instrumentation , Vaccines, DNA/administration & dosage , Adolescent , Adult , DNA, Viral/administration & dosage , DNA, Viral/immunology , Female , Hepatitis B Antibodies/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/adverse effects , Hepatitis B Vaccines/immunology , Humans , Immunity, Cellular , Immunization, Secondary , Injections, Jet/methods , Interferon-gamma/analysis , Interleukin-5/analysis , Male , Middle Aged , Vaccines, DNA/adverse effects , Vaccines, DNA/immunologyABSTRACT
A novel DNA vaccine against hepatitis B virus was administered intraepidermally by particle-mediated epidermal delivery (PMED) to 16 human subjects who demonstrated absent or non-sustainable responses to conventional hepatitis B vaccination. Eleven subjects received three doses of vaccine at 56-day intervals, and five subjects received only a single vaccination. Each dose of vaccine contained 4 microg of plasmid DNA encoding the hepatitis B surface antigen (HBsAg). The vaccine was safe and well tolerated. Remarkably, the DNA vaccine elicited antibody responses in 12 of the 16 subjects after a licensed subunit vaccine failed to induce a lasting response after >/=3 vaccinations. This study provides evidence in humans for protective immunogenicity of a particle-mediated DNA vaccine in subjects who have responded suboptimally to conventional vaccination.
