The cytoplasmic site of gene expression and use of virally encoded enzymes is a distinguishing feature of vaccinia virus and other poxvirus vector systems that probably accounts for their consistent ability to express foreign genes derived from a variety of prokaryotic, eukaryotic, and viral sources. This feature, together with their ability to stably integrate and package large amounts of DNA without loss of infetivity, their wide host range, and the development of simple and effective methods for isolating recombinant viruses, account for their diverse use and popularity. During the past year, we have continued to evaluate the highly attenuated MVA strain of vaccinia virus as an expression vector. Because of the inabilty of MVA to complete its replication cycle in human or other mammalian cells, it provides exceptional safety. A recombinant MVA that expresses the influenza virus hemagglutinin and nucleoprotein genes was constructed. Mice immunized with this recombinant virus developed a humoral and cell-mediated immune response and were protected against challenge with influenza virus. The protection was equal to or better than that achieved with a conventional replicating vaccinia virus vector.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000298-13
Application #
3746498
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
1994
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Domi, Arban; Moss, Bernard (2002) Cloning the vaccinia virus genome as a bacterial artificial chromosome in Escherichia coli and recovery of infectious virus in mammalian cells. Proc Natl Acad Sci U S A 99:12415-20
Stittelaar, K J; Kuiken, T; de Swart, R L et al. (2001) Safety of modified vaccinia virus Ankara (MVA) in immune-suppressed macaques. Vaccine 19:3700-9
McCart, J A; Ward, J M; Lee, J et al. (2001) Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res 61:8751-7
Hu, Y; Lee, J; McCart, J A et al. (2001) Yaba-like disease virus: an alternative replicating poxvirus vector for cancer gene therapy. J Virol 75:10300-8
Zhu, Y d; Rota, P; Wyatt, L et al. (2000) Evaluation of recombinant vaccinia virus--measles vaccines in infant rhesus macaques with preexisting measles antibody. Virology 276:202-13
Stittelaar, K J; Wyatt, L S; de Swart, R L et al. (2000) Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies. J Virol 74:4236-43
Men, R; Wyatt, L; Tokimatsu, I et al. (2000) Immunization of rhesus monkeys with a recombinant of modified vaccinia virus Ankara expressing a truncated envelope glycoprotein of dengue type 2 virus induced resistance to dengue type 2 virus challenge. Vaccine 18:3113-22
Durbin, A P; Cho, C J; Elkins, W R et al. (1999) Comparison of the immunogenicity and efficacy of a replication-defective vaccinia virus expressing antigens of human parainfluenza virus type 3 (HPIV3) with those of a live attenuated HPIV3 vaccine candidate in rhesus monkeys passively immunized with PIV3 J Infect Dis 179:1345-51
Nam, J H; Wyatt, L S; Chae, S L et al. (1999) Protection against lethal Japanese encephalitis virus infection of mice by immunization with the highly attenuated MVA strain of vaccinia virus expressing JEV prM and E genes. Vaccine 17:261-8
Wyatt, L S; Whitehead, S S; Venanzi, K A et al. (1999) Priming and boosting immunity to respiratory syncytial virus by recombinant replication-defective vaccinia virus MVA. Vaccine 18:392-7