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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #128897

Title: RECOMBINANT ADENOVIRUS ENCODING THE HA GENE FROM SWINE H3N2 INFLUENZA VIRUS PARTIALLY PROTECTS MICE FROM CHALLENGE WITH HETEROLOGOUS VIRUS: A/HK/1/68 (H3N2)

Author
item Tang, Min
item Harp, James
item Wesley, Ronald

Submitted to: Archives of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2002
Publication Date: N/A
Citation: N/A

Interpretive Summary: Swine influenza is a major cause of economic loss to U.S. pork producers. In addition, influenza viruses in swine act as a reservoir from which new strains of human influenza may arise. Current vaccines for swine are not fully effective because of the ability of the virus to recombine and produce new variants. To be more effective, a vaccine should induce immunity to components that are common to many virus variants. In the present study, we developed a vaccine by introducing the HA gene (common to most influenza viruses) into an adenovirus strain which by itself does not cause disease. We vaccinated mice intranasally with this vaccine and found that the mice produced antibodies against influenza virus. Furthermore, mice immunized with this vaccine survived influenza virus infection, while mice not vaccinated died from the infection. These results indicate that development of similar vaccines in swine may provide protection from swine influenza, thus reducing losses to producers as well as reducing the reservoir of viruses that contribute to human disease.

Technical Abstract: Since 1998, outbreaks of swine influenza caused by new swine influenza H3N2 virus (SIV) have presented as a new disease problem for the swine industry and are an issue of concern for public health. Currently an inactivated H3N2 virus vaccine has been conditionally licensed and is available for use in the United States. As a potential alternative vaccine, we report here developing recombinant adenoviral vaccine encoding the HA gene from swine H3N2 influenza virus. Two replication-defective recombinant adenoviruses were generated: (1) rAd-HA: recombinant adenovirus encoding the HA gene from swine H3N2 influenza virus, and (2) rAd-vector: a control recombinant adenovirus containing adenovirus and transfer plasmids without a foreign HA gene. We demonstrated that rAd-HA was capable of inducing influenza-specific antibodies. Mice given rAd-HA developed high titers of neutralizing SIV and hemagglutination inhibition (HI) antibodies in comparison to mice inoculated with rAd-vector or PBS as early as 2 weeks after immunization. Furthermore, neutralizing and HI antibodies were substantially increased in the mice given rAd-HA within the next 3 weeks following the 1st dose. More importantly, mice immunized with one or two doses of rAd-HA were protected from lethal challenge with heterologous virus, A/HK/1/68 (H3N2). A statistically significant (P<0.03) difference between survival rates of rAd-HA mice vs rAd-vector or PBS mice was observed. These results indicate that rAd-HA immunization may provide a novel and promising swine H3N2 influenza virus vaccination strategy.