Biotechnology and Bioprocess Engineering:BBE

The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
권호 표지

An Animal Model to Evaluate the Protective Efficacy of Haemophilus influenzae Type b Conjugate Vaccines

  • Published : 2004.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

An efficacy test of PRP (polyribosylribitol phosphate)-TT (Tetanus toxoid) conjugate vaccines was carried out using BALB/c mice as an animal model by inoculating Haemophilus in­fluenzae type b (Hib) with a virulence enhancement factor (VEF). Three administrations of the conjugate vaccines at 2-week intervals elicited a significantly high level of PRP antibodies (P>0.0001). The protective activity of the PRP immunization was challenged with either Hib with iron dextran (Hib/) or with a combination of mucin and hemoglobin (Hibmh) as a VEF. The me­dium lethal dose $(LD_{50})$ for Hibmh and Hibiwas measured as 10 CFU (Colony Forming Unit) and $2.5{\times}10^{8}$ CFU respectively. Each immunized animal was challenged with five or ten times the $LD_{50}$ level of bacteria with a VEF. A significant difference in mortality between the immunized and control mice (P> 0.01) was observed with the Hibmh challenge inoculation but not with the Hibi challenge inoculation. These results show that a combination of mucin and hemoglobin was able to enhance the virulence of Hib in BALB/c mice to cause a lethal infection, thus suggesting that BALB/c mice introduced to this method can be an effective model animal for testing the protective efficacy of H. influenzae conjugate vaccines.

Keywords

References

  1. Cochi, S. L., C. V. Broome, and A. W. Hightower (1985) Immunization of US children with Haemophilus influenzae type b polysaccharide vaccine. J. Am. Med. Ass. 253: 521-529 https://doi.org/10.1001/jama.253.4.521
  2. Coulehan, J. L., R. H. Michaels, K. E. Williams, D. K. Lemley, C. Q. Jr. North, T. K. Welty, and K. D. Rogers (1976) Bacterial meningitis in Navajo indians. Public Health Rep. 91: 464-468
  3. Tarr, P. I. and G. Peter (1978) Demographic factors in the epidemiology of Haemophilus influenzae meningitis in young children. J. Pediat. 92: 884-888 https://doi.org/10.1016/S0022-3476(78)80353-9
  4. Ward. J. (1991) Prevention of invasive Haemophilus influenzae type b disease: Lessons from vaccine efficacy trials. Vaccine 9: S17-24 https://doi.org/10.1016/0264-410X(91)90175-6
  5. Pittman M. (1933) The action of type-specific H. influenzae antiserum. J. Exp. Med. 58: 683-706 https://doi.org/10.1084/jem.58.6.683
  6. Onodera, M. (2002) Silicone rubber membrane bioreactors for bacterial cellulose production. Biotechnol. Bioprocess Eng. 10: 289-294
  7. Immunization practices advisory (ACIP) (1986) Update: Prevention of Haemophilus influenzae type b disease. Morbid. Mortal. Week. Rep. 35: 170
  8. Heath, P. T. and M. Fracp (1998) Haemophilus influenzae type b conjugate vaccines: A review of efficacy data. Pediatr. Infect. Dis. J. 17: S117-122 https://doi.org/10.1097/00006454-199809001-00005
  9. Burans, J. P., F. H. Kruszeski, M. Lynn, and M. Solotrovsky (1981) Kinetics of Haemophilus influenzae type b infection in normal and ribosom-immunized mice using intraperitoneal and intracerebral routes of inoculation. Br. J. Exp. Pathol. 62: 496-503
  10. Kaplan, S. L., E. O. Mason, Jr., and B. L. Wiedermann (1983) Role of adherence in the pathogenesis of Haemophilus influenzae type b infection in infant rats. Infec. Immun. 42: 612-617
  11. Smith, A. L., D. H. Smith, D. R. Averill, Jr., J. Marino, and E. R. Moxon (1983) Haemophilus influenzae type b bacteremia and meningitis infant rabbits after intranasal inoculation. J. Lab. Clin. Med. 102: 939-946
  12. Moxon, E. R., A. L. Smith, D. R. Averill, and D. H. Smith (1974) Haemophilus influenzae meningitis in infant rats after intranasal inoculation. J. Infect. Dis. 129: 154-162 https://doi.org/10.1093/infdis/129.2.154
  13. Marks, M. I., E. J. Ziegler, H. Douglas, and L. B. Corbeil (1982) Lethal Haemophilus influenzae type b infection in mice. Infection 10: 261-266 https://doi.org/10.1007/BF01640870
  14. Broueur, B. R., Y. Larose, P. Tsang, J. Hamel, F. Ashton, and A. Ryan (1985) Protection against infection with Neisseria meningitides group B serotype 2b by passive immunization with serotype specific monoclonal antibody. Infect. Immun. 50: 510-516
  15. Rodriguez, S. S., J. F. I. Bourzac, O. M. Chang, M. F. Medina, E. M. Carnago, and Y. L. Hernandez (1999) Virulence enhancement agents for Haemophilus influenzae type b infection in mice. Lab. Anim. Sci. 49: 95-98
  16. Halesy, N. A., T. L. Johansen, L. C. Bowman, and M. P. Glode (1983) Evaluation of the protective efficacy of Haemophilus influenzae type b vaccines in an animal model. Infec. Immun. 39: 1196-1200
  17. Brodeur, B. R., P. S. Tsang, J. Hamel, Y. Larose, and S. Montplaisir (1986) Mouse models of infection for Neisseria meningitides B, 2b and Haemophilus influenzae type b diseases. Can. J. Microbiol. 32: 33-37 https://doi.org/10.1139/m86-007
  18. Kristensen, K, and M. W. Bentzon (1992) Relation be-tween enzyme-linked immunoserbent assay and radioim-munoassay for detection of antibodies to the capsular polysaccharide of Haemophilus influenzae type b. APMIS 100: 142-146 https://doi.org/10.1111/j.1699-0463.1992.tb00853.x
  19. Farr, R. S. (1958) A quantitative immunochemical measurement of the primary interaction between I*BSA and antibody. J. Infect. Dis. 103: 239-262 https://doi.org/10.1093/infdis/103.3.239
  20. Kuo, J. S. C., N. Monji, R. S. Schwalbe, and D. W. McCoy (1981) A radioactive antigen-binding assay for the meas-urement of antibody to Haemophilus influenzae type b capsular polysaccharide. J. Immunol. Methods 43: 35-47 https://doi.org/10.1016/j.ymeth.2007.03.012
  21. Warlaw, A. C. (1985) Practical Statistics for Experimental Biologists. JohnWiley Wiley & Sons Ltd, USA
  22. Corbeil, G. A., C. P. Kenny, and G. Laverne (1976) Iron as a replacement for mucin in the establishment of meningococcal infection in mice. Can. J. Microbiol. 22: 832-838 https://doi.org/10.1139/m76-120
  23. Miller, C. P. (1933) Experimental meningococcal infection of mice. Science 78: 340-341 https://doi.org/10.1126/science.78.2024.340
  24. Ward, J., G. Brenneman, G. W. Leston, and W. L. Heyward (1990) Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska native infants. N. Engl. J. Med. 323: 1391-1401.
  25. Hong, H. J. and S. T. Kim (2002) Antibody engineering. Biotechnol. Bioprocess Eng. 7: 150-154 https://doi.org/10.1007/BF02932912
  26. Frasch, C. E. (1994) Regulatory perspectives in vaccine licensure. pp.435-453. In: Ellis R. W, D. W. Granoff (eds.). Development and Clinical Uses of Haemophilus b Conjugate Vaccine. Mercel Dekkar, New York, USA
  27. FDA approval of use of a new Haemophilus b conjugate vaccine and a combined diphtheria-tetanus-pertussis and Haemophilus b conjugate vaccine for infants and children. (1993) Morb. Mortal. Wkly. Rep. 42: 296-298
  28. Granoff, D. M. (2001) Assessing efficacy of Haemophilus influenzae type b combination vaccines. Clin. Infect. Dis. 33: S278-287 https://doi.org/10.1086/322563