Journal of General Virology, Vol 80, 1189-1198, Copyright © 1999 by Society for General Microbiology

ARTICLES

Recombinant Semliki Forest virus particles encoding the prME or NS1 proteins of louping ill virus protect mice from lethal challenge

MN Fleeton, BJ Sheahan, EA Gould, GJ Atkins and P Liljestrom
Microbiology and Tumorbiology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden

Recombinant Semliki Forest virus (rSFV) vaccines encoding louping ill virus (LIV) genes prME and NS1 were examined. Cells transfected with rSFV-prME RNA showed correct processing of the precursor prME and the release into the medium of M and E proteins in particulate form, whilst rSFV-NS1-transfected cells secreted glycosylated, heat-labile NS1 dimers. Mice immunized with rSFV particles produced antibodies against prME and NS1 that were mainly of the IgG2a subtype, indicating that a T-helper 1 immune response was induced. Immunization with prME- or NS1-encoding particles induced T-cell proliferation. Mice vaccinated intraperitoneally (i.p.) with rSFV-prME and/or rSFV-NS1 were significantly protected from lethal i.p. challenge by two strains of LIV, the virulent LI/31 strain, from which the commercial LIV vaccine is derived, and the less-virulent LI/I antibody-escape variant. Intranasal (i.n.) vaccination was protective for rSFV-prME only against LI/31 challenge and not against challenge with LI/I. Immunization with rSFV-NS1 was protective against i.p. and i.n. challenge with both virus strains when given i.p., but was not protective when given i.n. For unvaccinated mice infected with LIV, all animals showing clinical signs had severe degenerative and inflammatory lesions in the central nervous system. None of the rSFV-vaccinated mice that survived challenge showed central nervous system pathology, with the exception of mild leptomeningitis in a minority of LI/31-infected mice. This suggests that protection following immunization with rSFV must occur at early stages of LIV infection.

This article has been cited by other articles:

				J. R. Rodriguez-Madoz, K. H. Liu, J. I. Quetglas, M. Ruiz-Guillen, I. Otano, J. Crettaz, S. D. Butler, C. A. Bellezza, N. L. Dykes, B. C. Tennant, et al. Semliki Forest Virus Expressing Interleukin-12 Induces Antiviral and Antitumoral Responses in Woodchucks with Chronic Viral Hepatitis and Hepatocellular Carcinoma J. Virol., December 1, 2009; 83(23): 12266 - 12278. [Abstract] [Full Text] [PDF]

				M. N. E. Forsell, G. M. McInerney, P. Dosenovic, A. S. Hidmark, C. Eriksson, P. Liljestrom, C. Grundner, and G. B. Karlsson Hedestam Increased human immunodeficiency virus type 1 Env expression and antibody induction using an enhanced alphavirus vector J. Gen. Virol., October 1, 2007; 88(10): 2774 - 2779. [Abstract] [Full Text] [PDF]

				L. J. White, M. M. Parsons, A. C. Whitmore, B. M. Williams, A. de Silva, and R. E. Johnston An Immunogenic and Protective Alphavirus Replicon Particle-Based Dengue Vaccine Overcomes Maternal Antibody Interference in Weanling Mice J. Virol., October 1, 2007; 81(19): 10329 - 10339. [Abstract] [Full Text] [PDF]

				A. D. Garcia, C. A. Meseda, A. E. Mayer, A. Kumar, M. Merchlinsky, and J. P. Weir Characterization and Use of Mammalian-Expressed Vaccinia Virus Extracellular Membrane Proteins for Quantification of the Humoral Immune Response to Smallpox Vaccines Clin. Vaccine Immunol., August 1, 2007; 14(8): 1032 - 1044. [Abstract] [Full Text] [PDF]

				A. S. Hidmark, E. K. L. Nordstrom, P. Dosenovic, M. N. E. Forsell, P. Liljestrom, and G. B. Karlsson Hedestam Humoral Responses against Coimmunized Protein Antigen but Not against Alphavirus-Encoded Antigens Require Alpha/Beta Interferon Signaling J. Virol., July 15, 2006; 80(14): 7100 - 7110. [Abstract] [Full Text] [PDF]

				J. H. Aberle, S. W. Aberle, R. M. Kofler, and C. W. Mandl Humoral and Cellular Immune Response to RNA Immunization with Flavivirus Replicons Derived from Tick-Borne Encephalitis Virus J. Virol., December 15, 2005; 79(24): 15107 - 15113. [Abstract] [Full Text] [PDF]

				M. N. E. Forsell, Y. Li, M. Sundback, K. Svehla, P. Liljestrom, J. R. Mascola, R. Wyatt, and G. B. K. Hedestam Biochemical and Immunogenic Characterization of Soluble Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Expressed by Semliki Forest Virus J. Virol., September 1, 2005; 79(17): 10902 - 10914. [Abstract] [Full Text] [PDF]

				A. A. Onate, G. Donoso, G. Moraga-Cid, H. Folch, S. Cespedes, and E. Andrews An RNA Vaccine Based on Recombinant Semliki Forest Virus Particles Expressing the Cu,Zn Superoxide Dismutase Protein of Brucella abortus Induces Protective Immunity in BALB/c Mice Infect. Immun., June 1, 2005; 73(6): 3294 - 3300. [Abstract] [Full Text] [PDF]

				T. Hanke, C. Barnfield, E. G.-T. Wee, L. Agren, R. V. Samuel, N. Larke, and P. Liljestrom Construction and immunogenicity in a prime-boost regimen of a Semliki Forest virus-vectored experimental HIV clade A vaccine J. Gen. Virol., January 1, 2003; 84(2): 361 - 368. [Abstract] [Full Text] [PDF]

				M. Chen, K.-F. Hu, B. Rozell, C. Orvell, B. Morein, and P. Liljestrom Vaccination with Recombinant Alphavirus or Immune-Stimulating Complex Antigen Against Respiratory Syncytial Virus J. Immunol., September 15, 2002; 169(6): 3208 - 3216. [Abstract] [Full Text] [PDF]

				C. Brinster, M. Chen, D. Boucreux, G. Paranhos-Baccala, P. Liljestrom, F. Lemmonier, and G. Inchauspe Hepatitis C virus non-structural protein 3-specific cellular immune responses following single or combined immunization with DNA or recombinant Semliki Forest virus particles J. Gen. Virol., February 1, 2002; 83(2): 369 - 381. [Abstract] [Full Text] [PDF]

				J. J. DONNELLY, M. A. LIU, and J. B. ULMER Antigen Presentation and DNA Vaccines Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): S190 - 193. [Abstract] [Full Text] [PDF]

				M. N. Fleeton, P. Liljeström, B. J. Sheahan, and G. J. Atkins Recombinant Semliki Forest virus particles expressing louping ill virus antigens induce a better protective response than plasmid-based DNA vaccines or an inactivated whole particle vaccine J. Gen. Virol., March 1, 2000; 81(3): 749 - 758. [Abstract] [Full Text]

				G. J. Atkins, B. J. Sheahan, and P. Liljeström The molecular pathogenesis of Semliki Forest virus: a model virus made useful? J. Gen. Virol., September 1, 1999; 80(9): 2287 - 2297. [Full Text]