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. 1986 Jul;59(1):98–102. doi: 10.1128/jvi.59.1.98-102.1986

Genetic control of serum neutralizing-antibody response to rabies vaccination and survival after a rabies challenge infection in mice.

J W Templeton, C Holmberg, T Garber, R M Sharp
PMCID: PMC253043  PMID: 3086569

Abstract

Quantitative differences in serum neutralizing-antibody (SNAb) responses to rabies vaccination and survival after a rabies challenge infection between two inbred mice strains, C3H/J and C57BL/6J, were shown to be under genetic control. A 99% confidence limit calculated from the SNAb response titers of 14 C57BL/6J mice resulted in an upper limit for the SNAb response titer of C57BL/6J mice at 50.63. A SNAb titer less than or equal to 50.63 in response to rabies vaccination was assigned the phenotype of hyporesponder, and a SNAb titer greater than 50.63 in response to rabies vaccination was assigned the phenotype of hyperresponder in this study. The hyper-SNAb response to rabies vaccination and the higher frequency of survival after rabies challenge infection behave as Mendelian dominant alleles in F1 hybrids (C3H/J X C57BL/6J) and backcross (BC) (F1 [C3H/J X C57BL/6J] X C57BL/6J) progeny. Both a relatively hyper-SNAb response and a higher frequency of vaccine-inducible survival phenotypes occur in C3H/J mice. On the other hand, both the relatively hypo-SNAb response and a lower frequency of vaccine-inducible survival phenotypes behave as Mendelian recessive alleles and occur in C57BL/6J mice. C3H/J mice are H-2 Kk, and C57BL/6J mice are H-2 Kb. All three phenotypic traits (H-2 type, SNAb response, and survival after rabies challenge infection) segregate as independent (unlinked) monogenic traits in BC progeny (F1 [C3H/J X C57BL/6J] X C57BL/6J). The genetically controlled survival trait is inducible by rabies vaccination, but SNAb response is not a parameter that measures successful vaccine induction of preexposure protection from a rabies challenge infection in the BC progeny. The essential role of vaccination in developing preexposure protection in genetically responsive mice is confirmed, but indicates that in vitro measurements other than SNAb titers need to be developed to identify mice that have failed to achieve preexposure protection by rabies vaccination. This study confirms Lodmell's findings (D. L. Lodmell and B. Chesebro, J. Virol. 50:359-362, 1984; D. L. Lodmell, J. Exp. Med. 157:451-460, 1983) that susceptibility to rabies infection is genetically controlled in some mice strains. Additionally, this study indicates that conventional rabies vaccination even with more potent vaccines may not induce protection from infection in some genetically susceptible individuals.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berlin B. S., Mitchell J. R., Burgoyne G. H., Oleson D., Brown W. E., Goswick C., McCullough N. B. Rhesus diploid rabies vaccine (adsorbed), a new rabies vaccine. Results of initial clinical studies of preexposure vaccination. JAMA. 1982 Mar 26;247(12):1726–1728. [PubMed] [Google Scholar]
  2. Blancou J., Andral B., Andral L. A model in mice for the study of the early death phenomenon after vaccination and challenge with rabies virus. J Gen Virol. 1980 Oct;50(2):433–435. doi: 10.1099/0022-1317-50-2-433. [DOI] [PubMed] [Google Scholar]
  3. Cabasso V. J., Dobkin M. B., Roby R. E., Hammar A. H. Antibody response to a human diploid cell rabies vaccine. Appl Microbiol. 1974 Mar;27(3):553–561. doi: 10.1128/am.27.3.553-561.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Lodmell D. L., Bell J. F., Moore G. J., Raymond G. H. Comparative study of abortive and nonabortive rabies in mice. J Infect Dis. 1969 Jun;119(6):569–580. doi: 10.1093/infdis/119.6.569. [DOI] [PubMed] [Google Scholar]
  5. Lodmell D. L., Chesebro B. Murine resistance to street rabies virus: genetic analysis by testing second-backcross progeny and verification of allelic resistance genes in SJL/J and CBA/J mice. J Virol. 1984 May;50(2):359–362. doi: 10.1128/jvi.50.2.359-362.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lodmell D. L. Genetic control of resistance to street rabies virus in mice. J Exp Med. 1983 Feb 1;157(2):451–460. doi: 10.1084/jem.157.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Mifune K., Takeuchi E., Napiorkowski P. A., Yamada A., Sakamoto K. Essential Role of T cells in the postexposure prophylaxis of rabies in mice. Microbiol Immunol. 1981;25(9):895–904. doi: 10.1111/j.1348-0421.1981.tb00094.x. [DOI] [PubMed] [Google Scholar]
  8. Miller A., Morse H. C., 3rd, Winkelstein J., Nathanson N. The role of antibody in recovery from experimental rabies. I. Effect of depletion of B and T cells. J Immunol. 1978 Jul;121(1):321–326. [PubMed] [Google Scholar]
  9. Mittal K. K., Mickey M. R., Singal D. P., Terasaki P. I. Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation. 1968 Nov;6(8):913–927. doi: 10.1097/00007890-196811000-00006. [DOI] [PubMed] [Google Scholar]
  10. Nilsson M. R., Sant'anna O. A., Siqueira M., Nilsson T. T., Gennari M. Rabies virus immunity in genetically selected high- and low-responder lines of mice. Infect Immun. 1979 Jul;25(1):23–26. doi: 10.1128/iai.25.1.23-26.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Plotkin S. A., Wiktor T. J., Koprowski H., Rosanoff E. I., Tint H. Immunization schedules for the new human diploid cell vaccine against rabies. Am J Epidemiol. 1976 Jan;103(1):75–80. doi: 10.1093/oxfordjournals.aje.a112207. [DOI] [PubMed] [Google Scholar]
  12. Plotkin S. A., Wiktor T. Rabies vaccination. Annu Rev Med. 1978;29:583–591. doi: 10.1146/annurev.me.29.020178.003055. [DOI] [PubMed] [Google Scholar]
  13. Prabhakar B. S., Fischman H. R., Nathanson N. Recovery from experimental rabies by adoptive transfer of immune cells. J Gen Virol. 1981 Sep;56(Pt 1):25–31. doi: 10.1099/0022-1317-56-1-25. [DOI] [PubMed] [Google Scholar]
  14. Prabhakar B. S., Nathanson N. Acute rabies death mediated by antibody. Nature. 1981 Apr 16;290(5807):590–591. doi: 10.1038/290590a0. [DOI] [PubMed] [Google Scholar]
  15. Shah U., Jaswal G. S., Mansharamani H. J., Plotkin S. A., Wiktor T. J. Trial of human diploid cell rabies vaccine in human volunteers. Br Med J. 1976 Apr 24;1(6016):997–997. doi: 10.1136/bmj.1.6016.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sikes R. K., Cleary W. F., Koprowski H., Wiktor T. J., Kaplan M. M. Effective protection of monkeys against death from street virus by post-exposure administration of tissue-culture rabies vaccine. Bull World Health Organ. 1971;45(1):1–11. [PMC free article] [PubMed] [Google Scholar]
  17. Smith J. S. Mouse model for abortive rabies infection of the central nervous system. Infect Immun. 1981 Jan;31(1):297–308. doi: 10.1128/iai.31.1.297-308.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Smith J. S., Yager P. A., Baer G. M. A rapid reproducible test for determining rabies neutralizing antibody. Bull World Health Organ. 1973 May;48(5):535–541. [PMC free article] [PubMed] [Google Scholar]
  19. Turner G. S., Nicholson K. G., Tyrrell D. A., Aoki F. Y. Evaluation of a human diploid cell strain rabies vaccine: final report of a three year study of pre-exposure immunization. J Hyg (Lond) 1982 Aug;89(1):101–110. doi: 10.1017/s0022172400070583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wiktor T. J., Koprowski H. Monoclonal antibodies against rabies virus produced by somatic cell hybridization: detection of antigenic variants. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3938–3942. doi: 10.1073/pnas.75.8.3938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yelverton E., Norton S., Obijeski J. F., Goeddel D. V. Rabies virus glycoprotein analogs: biosynthesis in Escherichia coli. Science. 1983 Feb 11;219(4585):614–620. doi: 10.1126/science.6297004. [DOI] [PubMed] [Google Scholar]

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