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Baculovirus Induces an Innate Immune Response and Confers Protection from Lethal Influenza Virus Infection in Mice¹

Takayuki Abe^*, Hitoshi Takahashi^*,, Hiroyuki Hamazaki^*, Naoko Miyano-Kurosaki^*,, Yoshiharu Matsuura and Hiroshi Takaku^2,*,

^* Department of Industrial Chemistry and High Technology Research Center, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba, Japan; and Research Center for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

A recombinant baculovirus expressing the hemagglutinin gene of the influenza virus, A/PR/8/34 (H1N1), under the control of the chicken -actin promoter, was constructed. To determine the induction of protective immunity in vivo, mice were inoculated with the recombinant baculovirus by intramuscular, intradermal, i.p., and intranasal routes and then were challenged with a lethal dose of the influenza virus. Intramuscular or i.p. immunization with the recombinant baculovirus elicited higher titers of antihemagglutinin Ab than intradermal or intranasal administration. However, protection from a lethal challenge of the influenza virus was only achieved by intranasal immunization of the recombinant baculovirus. Surprisingly, sufficient protection from the lethal influenza challenge was also observed in mice inoculated intranasally with a wild-type baculovirus, as evaluated by reductions in the virus titer, inflammatory cytokine production, and pulmonary consolidations. These results indicate that intranasal inoculation with a wild-type baculovirus induces a strong innate immune response, which protects mice from a lethal challenge of influenza virus.

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