1887

Abstract

Live attenuated vaccines, developed with molecular genetical techniques, require new approaches for their quality control. To develop novel quality control tests that enhanced and extended existing procedures, the attenuated vaccine strain Ty21a and its parent strain Ty2 were characterized by pulsed-field gel electrophoresis (PFGE) and direct nucleotide sequence analysis. Mutant and parent strains were distinguished using fingerprints generated by the resolution on PFGE of chromosomal DNA digested with each of the enzymes l, or l. These fingerprints were stable through multiple passages of the vaccine strain and were identical from one batch of vaccine to another. It was also possible to distinguish between the mutant and parent strains by direct nucleotide sequence analysis of the gene. This analysis identified two base changes in the gene from strain Ty21a: a single base deletion causing a frameshift that would result in a truncated gene product, accounting for the phenotype; and a transition that eliminated an restriction site. The consequent change in the l fingerprint of the gene in strain Ty21a provided a rapid, PCR-based alternative to the use of differential media or biochemical assays for the identification of the vaccine strain.

Loading

Article metrics loading...

/content/journal/micro/10.1099/13500872-141-8-1993
1995-08-01
2021-08-05
Loading full text...

Full text loading...

/deliver/fulltext/micro/141/8/mic-141-8-1993.html?itemId=/content/journal/micro/10.1099/13500872-141-8-1993&mimeType=html&fmt=ahah

References

  1. Ashcroft M.T., Morrison-Ritchie J., Nicholson C.C. 1964; Controlled field trial in British Guyana school-children of heat- killed-phenolized and acetone-killed lyophilized typhoid vaccines. Am J Hyg 79:196–206
    [Google Scholar]
  2. Black R.E., Levine M.M., Ferreccio C., Clements M.L., Lanata C., Rooney J., Germanier R. Chilean Typhoid Committee 1990; Efficacy of one or two doses of Ty21aSalmonella typhivaccine in enteric-coated capsules in a controlled field trial. Vaccine 8:81–84
    [Google Scholar]
  3. Bohm H., Karch H. 1992; DNA fingerprinting ofEscherichia coli0157: H7 strains by pulsed-field gel electrophoresis. J Clin Microbiol 30:2169–2172
    [Google Scholar]
  4. Bygraves J.A., Maiden M.C.J. 1992; Analysis of the clonal relationships between strains ofNeisseria meningitidis by pulsed field gel electrophoresis. J Gen Microbiol 138:523–531
    [Google Scholar]
  5. Cardenas L., Clements J.D. 1992; Oral immunization using live attenuatedSalmonella spp. as carriers of foreign antigens. Clin Microbiol Rev 5:328–342
    [Google Scholar]
  6. Carle G.F., Frank M., Olson M.V. 1986; Electrophoretic separations of large DNA molecules by periodic inversion of the electric field. Science 232:64–68
    [Google Scholar]
  7. Chatfield S.N., Strugnell R.A., Dougan G. 1989; LiveSalmonella as vaccines and carriers of foreign antigenic determinants. Vaccine 7:495–498
    [Google Scholar]
  8. Chatfield S.N., Charles I.G., Makoff A.J., Oxer M.D., Dougan G., Pickard D., Slater D., Fairweather N.F. 1992; Use of thenirB promoter to direct the stable expression of heterologous antigens inSalmonella oral vaccine strains: development of a singledose oral tetanus vaccine. Biotechnology 10:888–892
    [Google Scholar]
  9. Clements J.D., El-Morshidy S. 1984; Construction of a potential live oral bivalent vaccine for typhoid fever and cholera- Escherichia coli related diarrhoea. Infect Immun 46:564–569
    [Google Scholar]
  10. Dougan G. 1994; The molecular basis for the virulence of bacterial pathogens: implications for oral vaccine development. Microbiology 140:215–224
    [Google Scholar]
  11. Dougan G., Maskell D., Pickard D., Hormaeche C. E. 1987; Isolation of stablearoA mutants ofSalmonella typhi Ty2: properties and preliminary characterization in mice. Mol & Gen Genet 207:402–05
    [Google Scholar]
  12. Dougan G., Hofnung M., Lanzavecchia A., Leclerc C. 1990; Immune response to proteins with recombinant epitopes, perspectives for vaccines. In Conferences Philipe laudat 1990 INSERM pp. 171–220 Paris:: INSERM.;
    [Google Scholar]
  13. Drake J.W. 1976; The biochemistry of mutagenesis. Anna Rev Biochem 45:11–37
    [Google Scholar]
  14. Embley T.M. 1991; The linear PCR reaction: a simple and robust method for sequencing amplified rRNA genes. Lett Appl Microbiol 13:171–174
    [Google Scholar]
  15. Fineschi N., Pellegrini V., Zuckerman A.J., Cavalier! F. 1992; Assessment of inactivation of hepatitis A vaccine by compound PCR. J Virol Methods 39:157–163
    [Google Scholar]
  16. Formal S.B., Baron L.S., Kopecko D.J., Washington C., Powell C., Life C.A. 1981; Construction of a potential bivalent vaccine strain: introduction ofShigella sonnei form I antigen genes into thegalE Salmonella typhi Ty21a typhoid vaccine strain. Infect Immun 34:746–750
    [Google Scholar]
  17. Forrest B.D. 1991; Oral typhoid vaccine Ty21a. Eancet 338:1455–1456
    [Google Scholar]
  18. Forrest B.D., LaBrooy J.T., Beyer L., Dearlove C.E., Shearman D.J. 1991; The human humoral immune response toSalmonella typhi Ty21a. J Infect Dis 163:336–345
    [Google Scholar]
  19. Germanier R., Furer E. 1975; Isolation and characterization ofgalE mutant Ty21a ofSalmonella typhi:a candidate for a live, oral typhoid vaccine. J Infect Dis 131:553–558
    [Google Scholar]
  20. Germanier R., Furer E. 1983; Characteristics of the attenuated oral vaccine strainS. typhi Ty21a. Dev Biol Stand 53:3–7
    [Google Scholar]
  21. Gilman R.H., Hornick R.B., Woodward W.E., DuPont H.L., Snyder M.J., Levine M.M., Libonati J.P. 1977; Evaluation of a UDP-glucose-4-epimeraseless mutant ofSalmonella typhi as a live oral vaccine. J Infect Dis 136:717–723
    [Google Scholar]
  22. Hirschel B., WUthrich R., Somaini B., Steffen R. 1985; InefBcacy of the commercial live oral Ty21a vaccine in the prevention of typhoid fever. Eur J Clin Microbiol 4:295–298
    [Google Scholar]
  23. Hone D.M., Attridge S.R., Forrest B. 1988; AgalE via (Vi antigen-negative) mutant ofSalmonella typhi Ty2 retains virulence in humans. Infect Immun 56:1326–1333
    [Google Scholar]
  24. Hone D.M., Harris A.M., Chatfield S., Dougan G., Levine M.M. 1991; Construction of genetically defined doublearo mutants ofSalmonella typhi. . Vaccine 9:810–816
    [Google Scholar]
  25. Houng H.H., Kopecko D.J., Baron L.S. 1990; Molecular cloning and physical and functional characterization of theSalmonella typhimurium andSalmonella typhi galactose utilization operons. J Bacteriol 172:4392–4398
    [Google Scholar]
  26. Lemaire H.G., Mueller-Hill B. 1986; Nucleotide sequences of thegalE and thegalT genes ofE. coli. . Nucleic Acids Res 14:7705–7711
    [Google Scholar]
  27. Levine M.M., Kaper J.B. 1993; Live oral vaccines against cholera: an update. Vaccine 11:207–212
    [Google Scholar]
  28. Levine M.M., Ferreccio C., Black R.E., Germanier R. Chilean Typhoid Committee 1987; Large-scale field trial of Ty21a live oral typhoid vaccine in enteric-coated capsule formulation. Lancet I:1049–1052
    [Google Scholar]
  29. Liu S.L., Sanderson K.E. 1992; A physical map of theSalmonella typhimurium LT2 genome made by usingXhcH analysis. J Bacteriol 174:1662–1672
    [Google Scholar]
  30. Liu S.L, Sanderson K.E. 1993; TheXbal-BlnI-CeuI genomic cleavage map ofSalmonella typhimurium LT2 determined by double digestion, end labelling, and pulsed-field gel electrophoresis. J Bacteriol 175:4104–4120
    [Google Scholar]
  31. Maniatis T., Fritsch E.F., Sambrook J. 1982 Molecular Cloning-, a Laboratory Manual Cold Spring Harbor, NY:: Cold Spring Harbor Laboratory.;
    [Google Scholar]
  32. Metzger M., Bellemann P., Bugert P., Geider K. 1994; Genetics of galactose metabolism ofEnvinia amylovora and its influence on polysaccharide-synthesis and virulence of the fire blight pathogen. J Bacteriol 176:450–459
    [Google Scholar]
  33. Mori T. 1994; A simple method for genetic differentiation of the AIK-C vaccine strain from wild strains of measles virus. Biologicals 22:179–185
    [Google Scholar]
  34. Murphy J.R., Grez L., Schlesinger L., Ferreccio C., Baqar S., Munoz C., Wasserman S.S., Losonsky G., Olson J.G., Levine M.M. 1991; Immunogenicity ofSalmonella typhi Ty21a vaccine for young children. Infect Immun 59:4291–4293
    [Google Scholar]
  35. Polish Typhoid Committee 1966; Controlled field trials and laboratory studies on the effectiveness of typhoid vaccines in Poland. Bull WHO 34:211–222
    [Google Scholar]
  36. Ripley L.S., Clark A., deBoer J.G. 1986; Spectrum of spontaneous frameshift mutations: sequences of bacteriophage T4 rll gene frameshifts. J Mol Biol 191:601–613
    [Google Scholar]
  37. Scherba G., Jin L., Schnitzlein W.M., Vodkin M.H. 1992; Differential polymerase chain reaction for detection of wild-type and a vaccine strain of Aujeszky's disease (pseudorabies) virus. J Virol Methods 38:131–143
    [Google Scholar]
  38. Schwartz D.C., Cantor C.R. 1984; Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell 37:67–75
    [Google Scholar]
  39. Simanjuntak C.H., Paleologo F.P., Punjabi N.H., Darmowigoto R., Soeprawoto Totosudirjo H, Haryanto P., Suprijanto E., Witham N.D., Hoffman S.L. 1991; Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet 338:1055–1059
    [Google Scholar]
  40. Takeda N., Sakae K., Agboatwalla M., Isomura S., Hondo R., Inouye S. 1994; Differentiation between wild and vaccine-derived strains of poliovirus by stringent microplate hybridization of PCR products. J Clin Microbiol 32:202–204
    [Google Scholar]
  41. Wahdan M.H., Serie C., Cerisier Y., Sallam S., Germanier R. 1982; A controlled field trial of liveSalmonella tjphi strain Ty21a oral vaccine against typhoid: three-year results. J Infect Dis 145:292
    [Google Scholar]
  42. Yugoslav Typhoid Commission 1964; A controlled field trial of the effectiveness of acetone-dried and inactivated and heat-phenol- inactivated typhoid vaccines in Yugoslavia. Bull WHO 30:623–630
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/13500872-141-8-1993
Loading
/content/journal/micro/10.1099/13500872-141-8-1993
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error