DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations.

• DOI: 10.1073/pnas.90.24.11478
• Publication Date: 2006-05-31T12:36:45Z
• Authors: E F Fynan; R G Webster; D H Fuller; J R Haynes; J C Santoro; H L Robinson
• Keywords: Hemagglutinin Glycoproteins; Influenza Virus; Genes, Viral; Restriction Mapping; Hemagglutinins, Viral; Hemagglutinin Glycoproteins, Influenza Virus; Transfection; Injections, Intramuscular; Cell Line; Injections; Mice; 03 medical and health sciences; 0302 clinical medicine; Orthomyxoviridae Infections; Viral Envelope Proteins; Medicine and Health Sciences; Animals; Viral; Inbred BALB C; Intramuscular; Mice, Inbred BALB C; Mucous Membrane; Life Sciences; DNA; 3. Good health; Hemagglutinins; Genes; Influenza A virus; Influenza in Birds; DNA, Viral; Injections, Intravenous; Intravenous; Chickens

Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been tested for their ability to raise protective immunity against lethal influenza challenges of the same subtype. In trials using two inoculations of from 50 to 300 micrograms of purified DNA in saline, 67-95% of test mice and 25-63% of test chickens have been protected against a lethal influenza challenge. Parenteral routes of inoculation that achieved good protection included intramuscular and intravenous injections. Successful mucosal routes of vaccination included DNA drops administered to the nares or trachea. By far the most efficient DNA immunizations were achieved by using a gene gun to deliver DNA-coated gold beads to the epidermis. In mice, 95% protection was achieved by two immunizations with beads loaded with as little as 0.4 micrograms of DNA. The breadth of routes supporting successful DNA immunizations, coupled with the very small amounts of DNA required for gene-gun immunizations, highlight the potential of this remarkably simple technique for the development of subunit vaccines.