Vaccination with polymerase chain reaction-generated linear expression cassettes protects mice against lethal influenza A challenge.
The feasibility of a linear expression cassette (LEC)-based influenza A DNA vaccine was demonstrated in mice, using a lethal dose (LD90) of a mouse-adapted A/Hong Kong/8/68 (H3N2) influenza strain. LECs expressing hemagglutinin (HA) from either the homotypic H3N2 or the heterotypic H1N1 (A/Puerto Rico/8/34) influenza virus were produced by polymerase chain reaction and either phosphodiester- or phosphorothioate-modified oligonucleotide primers. Survival subsequent to lethal viral challenge was used as a primary end point; weight loss was the secondary end point. Survival and weight loss data showed that protection can be achieved in mice with 50 microg of phosphate-buffered saline-formulated LEC DNA or 2 microg of Vaxfectin-formulated LEC DNA. Survival correlated with neutralizing antibody titers (hemagglutination inhibition, HAI); titers obtained after vaccination with LEC were equivalent to those obtained with HA (H3N2) plasmid DNA control. Vaccination with heterotypic H1 HA-LEC DNA provided no protection against viral challenge.
Vilalta
Adrián
A
Vical, San Diego, CA 92121, USA. avilalta@vical.com
Jimenez
Gretchen
G
Rusalov
Denis
D
Planchon
Rodrick
R
Lalor
Peggy
P
Carner
Kristin
K
Chaplin
Jennifer A
JA
Komai
Michael
M
Manthorpe
Marston
M
Kaslow
David C
DC
Rolland
Alain
A
D000818:Animals; D002460:Cell Line; D004285:Dogs; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D011817:Rabbits; D014422:Turkeys; D019444:Vaccines, DNA / Q000276:immunology*
D007252:Influenza Vaccines; D019444:Vaccines, DNA