Summary
Mice were vaccinated with recombinant vaccinia virus (rVac) expressing the glycoprotein (G), nucleoprotein (N), phosphoprotein (NS) or matrix protein (M) of rabies virus and their resistance to peripheral lethal infection with street rabies virus was examined. Mice vaccinated with rVac-G or rVac-N developed strong antibody responses to the corresponding proteins and essentially all mice survived challenge infection. Mice vaccinated with rVac-NS or rVac-M developed only a slight antibody response, however, a significant protection (59%) was observed in the rVac-NS-vaccinated mice, whereas rVac-M-vaccinated mice were not protected. No anti-G antibodies were detected in the sera of mice which had been vaccinated with rVac-N or rVac-NS and survived challenge infection. Passive transfer of anti-N monoclonal antibodies (MAbs) recognizing an epitope located on amino acids 1–224 of the protein prior to challenge resulted in significant protection, although the protection was not complete even with a high amount of antibodies. In contrast, none of the mice given MAbs recognizing an epitope of amino acids 247–415 or F(ab′)2 fragments from a protective MAb IgG were protected. Administration of anti-CD 8 MAb to rVac-N-vaccinated mice showed no significant effect on protection. Our observations suggest that a considerable part of the protection achieved by the vaccination with rVac-N can be ascribed to the intact anti-N antibodies recognizing an epitope located on amino acids 1–224 of the protein.
Similar content being viewed by others
References
Blancou J (1988) Epizootiology of rabies: Eurasia and Africa. In: Campbell JB, Charlton KM (eds) Rabies. Kluwer Academic Publishers, Boston, pp 243–265
Boere WA, Benaissa-Trouw MBJ, Harmsen T, Erich T, Kraaijeveld CA, Snippe H (1985) Mechanisms of monoclonal antibody-mediated protection against virulent Semliki Forest virus. J Virol 54: 546–551
Brochier B, Thomas I, Bauduin B, Leveau T, Pastoret PP, Languet B, Chappuis G, Desmettre P, Blancou J, Artois M (1990) Use of a vaccinia-rabies recombinant virus for the oral vaccination of foxes against rabies. Vaccine 8: 101–104
Bunschoten H, Gore M, Claassen IJTM, Uytdehaag FGCM, Dietzschold B, Wunner WH, Osterhaus ADME (1989) Characterization of a new virus-neutralizing epitope that denotes a sequential determinant on the rabies virus glycoprotein. J Gen Virol 70: 291–298
Burton DR, Woof JM (1992) Human antibody effector function. In: Dixon FJ (ed) Advances in immunology, vol 51. Academic Press, New York, pp 1–84
Celis E, Wiktor T, Dietzschold B, Koprowski H (1985) Amplification of rabies virus-induced stimulation of human T-cell lines and clones by antigen-specific antibodies. J Virol 56: 426–433
Chakrabarti S, Brechling K, Moss B (1985) Vaccinia virus expression vector: coexpression of β-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol 5: 3403–3409
Cox JH, Dietzschold B, Schneider LG (1977) Rabies virus glycoprotein. II. Biological and serological characterization. Infect Immun 16: 754–759
Dietzschold B, Wang H, Rupprecht CE, Celis E, Tollis M, Ertl H, Heber-Katz E, Koprowski H (1987) Induction of protective immunity against rabies by immunization with rabies virus ribonucleoprotein. Proc Natl Acad Sci USA 84: 9165–9169
Dietzschold B, Gore M, Ertl H, Celis E, Otvos Jr L, Koprowski H (1989) Analysis of protective immune mechanisms induced by rabies nucleoprotein. In: Mahy WJ, Kolakofski D (eds) Genetics and pathogenicity of negative-strand viruses. Elsevier, New York, pp 295–305
Ertl HC, Dietzschold B, Gore M, Otvos Jr L, Larson JK, Wunner WH, Koprowski H (1989) Induction of rabies virus-specific T-helper cells by synthetic peptides that carry dominant T-helper cell epitopes of the viral ribonucleoprotein. J Virol 63: 2885–2892
Esposito JJ, Brechling K, Baer G, Moss B (1987) Vaccinia virus recombinants expressing rabiesvirus glycoprotein protect against rabies. Virus Genes 1: 7–21
Ey PL, Prowse SJ, Jenkin CR (1978) Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry 15: 429–436
Fekadu M, Sumner JW, Shaddock JH, Sanderlin DW, Baer GM (1992) Sickness and recovery of dogs challenged with a street rabies virus after vaccination with a vaccinia virus recombinant expressing rabies virus N protein. J Virol 66: 2601–2604
Fu ZF, Dietzschold B, Schumacher CL, Wunner WH, Ertl H, Koprowski H (1991) Rabies virus nucleoprotein expressed in and purified from insect cells is efficacious as a vaccine. Proc Natl Acad Sci USA 88: 2001–2005
Grosfeld H, Velan B, Leitner M, Cohen S, Lustig S, Lachmi BE, Shafferman A (1989) Semliki Forest virus E2 envelope epitopes induce a nonneutralizing humoral response which protects mice against lethal challenge. J Virol 63: 3416–3422
Hiramatsu K, Mifune K, Mannen K, Nishizono A, Kawano H, Ito Y, Kawai A (1992) Mapping of the antigenic determinants recognized by monoclonal antibodies against the M 2 protein of rabies virus. Virology 187: 472–479
Kawano H, Mifune K, Ohuchi M, Mannen K, Cho S, Hiramatsu K, Shichijo A (1990) Protection against rabies in mice by a cytotoxic T cell clone recognizing the glycoprotein of rabies virus. J Gen Virol 71: 281–287
Kieny MP, Lathe R, Drillien R, Spehner D, Skory S, Schmitt D, Wikter TJ, Koprowski H, Lecocq JP (1984) Expression of rabies virus glycoprotein from a recombinant vaccinia virus. Nature 312: 163–166
Koprowski H (1973) Vaccine for man prepared in human diploid cells. In: Kaplan MM, Koprowski H (eds) Laboratory techniques in rabies, 3rd edn. World Health Organization, Geneva, pp 256–260
Lafon M, Wiktor TJ, MacFarlan RI (1983) Antigenic sites on the CVS rabies virus glycoprotein: analysis with monoclonal antibodies. J Gen Virol 64: 843–851
Lafon M, Lafage M (1987) Antiviral activity of monoclonal antibodies specific for the internal proteins N and NS of rabies virus. J Gen Virol 68: 3113–3123
Lafon M, Lafage M, Martinez-Arends A, Ramirez R, Vuillier F, Charron D, Lotteau V, Scott-Algara D (1992) Evidence for a viral superantigen in humans. Nature 358: 507–510
Larson JK, Wunner WH, Otvos Jr L, Ertl HC (1991) Identification of an immunodominant epitope within the phosphoprotein of rabies virus that is recognized by both class I - and class II - restricted T cells. J Virol 65: 5673–5679
Lodmell DL, Sumner JW, Esposito JJ, Bellini WJ, Ewalt LC (1991) Raccoon poxvirus recombinants expressing the rabies virus nucleoprotein protect mice against lethal rabies virus infection. J Virol 65: 3400–3405
Mannen K, Hiramatsu K, Mifune K, Sakamoto S (1991) Conserved nucleotide sequences of rabies virus cDNA encoding the nucleoprotein. Virus Genes 5: 69–73
Mifune K, Shichijo A, Makino Y, Takeuchi E, Yamada A, Sakamoto K (1980) A mouse model for the pathogenesis and postexposure prophylaxis of rabies. Microbiol Immunol 24: 835–845
Mifune K, Mannen K, Minamoto N, Arai YT (1986) Further studies on an improved haemagglutination inhibition test with higher sensitivity for rabies virus antibody. Bull World Health Organ 64: 133–137
Ouchterlony Ö (1958) Diffusion-in-gel methods for immunological analysis. In: Kallos P (ed) Progress in allergy, vol V. Karger, Basel, pp 1–78
Parham P (1986) Preparation and purification of active fragments from mouse monoclonal antibodies. In: Weir DM et al (eds) Handbook of experimental immunology, vol I: Immunochemistry. Blackwell Scientific Publications, Oxford, pp 14.1–14.23
Perrin P, Joffret ML, Leclerc C, Oth D, Sureau P, Thibodeau L (1988) Interleukin 2 increases protection against experimental rabies. Immunobiology 177: 199–209
Prevec L, Campbell JB, Christie BS, Belbeck L, Graham FI (1990) A recombinant human adenovirus vaccine against rabies. J Infect Dis 161: 27–30
Saleh F, Gard GP, Compans RW (1979) Synthesis of tacaribe viral proteins. Virology 93: 369–376
Smith AL, Tignor GH, Mifune K, Motohashi T (1977) Isolation and assay of rabies serogroup viruses in CER cells. Intervirology 8: 92–99
Smith JS, Yager PA, Baer GM (1973) A rapid reproducible test for determining rabies neutralizing antibody. Bull World Health Organ 48: 535–541
Stanley J, Cooper SJ, Griffin DE (1986) Monoclonal antibody cure and prophylaxis of lethal Sindbis virus encephalitis in mice. J Virol 58: 107–115
Sugimoto M, Yasuda A, Miki K, Morita M, Suzuki K, Uchida N, Hashizume S (1985) Gene structures of low-neurovirulent vaccinia virus LC 16 mO, and their Lister original (LO) strains. Microbiol Immunol 29: 421–428
Sumner JW, Fekadu M, Shaddock JH, Esposito JJ, Bellini WJ (1991) Protection of mice with vaccinia virus recombinants that express the rabies nucleoprotein. Virology 183: 703–710
Tan CHC, Yap EH, Singh M, Deubel V, Chan YC (1990) Passive protection studies in mice with monoclonal antibodies directed against the non-structural protein NS 3 of dengue 1 virus. J Gen Virol 71: 745–748
Wiktor TJ, MacFarlan RI, Reagan KJ, Dietzschold B, Curtis PJ, Wunner WH, Kieny MP, Lathe R, Lecocq JP, Mackett M, Moss B, Koprowski H (1984) Protection from rabies by a vaccinia virus recombinant containing the rabies virus glycoprotein gene. Proc Natl Acad Sci USA 81: 7194–7198
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takita-Sonoda, Y., Fujii, H., Mifune, K. et al. Resistance of mice vaccinated with rabies virus internal structural proteins to lethal infection. Archives of Virology 132, 51–65 (1993). https://doi.org/10.1007/BF01309843
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01309843