Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans.
The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine expressed by next-generation vectors. These new vectors can improve gene expression, but they are also efficiently produced on large scales and comply with regulatory guidelines by avoiding antibiotic resistance genes. In addition, a new needle-free delivery of the vaccine, convenient for mass vaccinations, was compared with intradermal needle injection followed by electroporation. We report that when our DNA vaccine is expressed by the new vectors and delivered to the skin with the needle-free device in the rabbit model, it can elicit an antibody response with the same titers as a conventional vector with intradermal electroporation. The needle-free delivery is already in use for traditional protein vaccines in pigs but should be considered as a practical alternative for the mass administration of broadly protective influenza DNA vaccines.
a Virus Research and Development Laboratory ; Department of Microbiological Diagnostic and Virology; Statens Serum Institut ; Copenhagen , Denmark.
Marie
M
Borggren
Jens
J
Nielsen
Karoline
K
Bragstad
Ingrid
I
Karlsson
Jesper S
JS
Krog
James A
JA
Williams
Anders
A
Fomsgaard
D000279:Administration, Cutaneous; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000662:veterinary*; D011817:Rabbits; D013552:Swine; D013553:Swine Diseases / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D019444:Vaccines, DNA
BSA, bovine serum albumin; DK, Denmark; DNA vaccine; DNA, DeoxyriboNucleic Acid; ELISA, Enzyme Linked Immunosorbent Assay; EP, electroporation; FCS, fetal calf serum; HA, hemagglutinin; HAI, hemagglutination inhibition assay; HAU, hemagglutination units; HI, hemagglutination inhibition; IDAL®, IntraDermal Application of Liquids®; IgG, immunoglobulin G; M, matrix protein; MDCK cells, Madin-Darby Canine Kidney epithelial cells; NA, neuraminidase; NP, nucleoprotein; NTC8385-VA1; NTC9385R; NZW, New Zealand White; PBS, phosphate buffered saline; RDE, receptor destroying enzyme; SEM, standard error mean; TMB, tetramethylbenzidine; US, the United States; WHO, world health organization; bp, base pair; i.d., intra-dermal; influenza; needle-free; polyvalent; tPA, tissue plasminogen activator