Baculovirus vectors elicit antigen-specific immune responses in mice.
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.
Istituto di Ricerche di Biologia Moleculare, Via Pontina Km 30,600, 00040 Pomezia, Italy.
Andrea
A
Facciabene
Luigi
L
Aurisicchio
Nicola
N
La Monica
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016367:Baculoviridae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000914:Antibodies, Viral; D002272:Carcinoembryonic Antigen; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus