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Journal of Virology, August 2004, p. 8663-8672, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8663-8672.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Baculovirus Vectors Elicit Antigen-Specific Immune Responses in Mice

Istituto di Ricerche di Biologia Moleculare, 00040 Pomezia, Italy¹

Received 11 December 2003/ Accepted 6 April 2004

To characterize the induction of antigen-specific immune response mediated by baculovirus, vectors expressing the E2 glycoprotein of hepatitis C virus or the carcinoembryonic antigen (CEA) under the control of the cytomegalovirus immediate-early promoter-enhancer were constructed. Additionally, a baculovirus vector encoding the E2 glycoprotein (Bac-G-E2) and expressing vesicular stomatitis virus glycoprotein (VSV-G) in the viral envelope was generated by inserting the VSV-G coding sequence downstream of the polyhedrin promoter. Mice were subjected to intramuscular, intranasal, or subcutaneous inoculations with Bac-E2 and the cellular immune response was monitored by ELISPOT and intracellular staining. Additionally, humoral response was monitored by titrating anti-E2 antibodies. Induction of a measurable anti-E2 T-cell response was observed only after intramuscular injection and was predominantly CD8⁺ specific. The immunogenic properties of baculovirus as vaccine vector were not restricted to E2 because a CEA-specific CD4⁺ T-cell response was observed upon intramuscular injection of Bac-CEA. Interestingly, the Bac-G-E2 vector was shown to be a more efficient immunogen than Bac-E2, in view of the 10-fold difference in the minimal dose required to elicit a measurable T-cell response upon intramuscular injection. Induction of inflammatory cytokines such as gamma interferon, tumor necrosis factor alpha, and interleukin-6 was detected as early as 6 h postinjection of Bac-G-E2. Most importantly, both vectors elicited CD8⁺ T cells with effector function capable of lysing target cells loaded with a hepatitis C virus-specific epitope. Additionally, enhanced NK cytolytic activity was detected in immunized mice. Thus, these results further demonstrate that baculovirus may be considered a useful vector for gene therapy.

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