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. 1989 Jun;86(11):4240–4243. doi: 10.1073/pnas.86.11.4240

Interleukin 2 acts as an adjuvant to increase the potency of inactivated rabies virus vaccine.

J H Nunberg 1, M V Doyle 1, S M York 1, C J York 1
PMCID: PMC287426  PMID: 2786210

Abstract

Interleukin 2 (IL-2) occupies a central position in the cascade of events involved in the immune response. We were interested in determining whether IL-2 could function as an adjuvant to vaccination, to increase the immune response to vaccine immunogens. Using the National Institutes of Health test for rabies vaccine potency, we found that daily systemic administration of IL-2 in conjunction with inactivated rabies virus can increase the potency of vaccination in outbred mice at least 25-fold, as measured by survival following challenge with virulent rabies virus. Enhanced protection is not correlated with an increase in virus-neutralizing antibody titers, and we suggest that IL-2 acts to increase the cellular immune response to vaccination.

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Selected References

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  1. Abelseth M. K. Propagation of Rabies Virus in Pig Kidney Cell Culture. Can Vet J. 1964 Apr;5(4):84–87. [PMC free article] [PubMed] [Google Scholar]
  2. Basham T., Smith W., Lanier L., Morhenn V., Merigan T. Regulation of expression of class II major histocompatibility antigens on human peripheral blood monocytes and Langerhans cells by interferon. Hum Immunol. 1984 Jun;10(2):83–93. doi: 10.1016/0198-8859(84)90075-2. [DOI] [PubMed] [Google Scholar]
  3. Coffman R. L., Seymour B. W., Lebman D. A., Hiraki D. D., Christiansen J. A., Shrader B., Cherwinski H. M., Savelkoul H. F., Finkelman F. D., Bond M. W. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988 Feb;102:5–28. doi: 10.1111/j.1600-065x.1988.tb00739.x. [DOI] [PubMed] [Google Scholar]
  4. Craven D. E., Awdeh Z. L., Kunches L. M., Yunis E. J., Dienstag J. L., Werner B. G., Polk B. F., Syndman D. R., Platt R., Crumpacker C. S. Nonresponsiveness to hepatitis B vaccine in health care workers. Results of revaccination and genetic typings. Ann Intern Med. 1986 Sep;105(3):356–360. doi: 10.7326/0003-4819-105-3-356. [DOI] [PubMed] [Google Scholar]
  5. Dietzschold B., Tollis M., Rupprecht C. E., Celis E., Koprowski H. Antigenic variation in rabies and rabies-related viruses: cross-protection independent of glycoprotein-mediated virus-neutralizing antibody. J Infect Dis. 1987 Nov;156(5):815–822. doi: 10.1093/infdis/156.5.815. [DOI] [PubMed] [Google Scholar]
  6. Dietzschold B., Wang H. H., Rupprecht C. E., Celis E., Tollis M., Ertl H., Heber-Katz E., Koprowski H. Induction of protective immunity against rabies by immunization with rabies virus ribonucleoprotein. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9165–9169. doi: 10.1073/pnas.84.24.9165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dietzschold B., Wiktor T. J., Macfarlan R., Varrichio A. Antigenic structure of rabies virus glycoprotein: ordering and immunological characterization of the large CNBr cleavage fragments. J Virol. 1982 Nov;44(2):595–602. doi: 10.1128/jvi.44.2.595-602.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fauci A. S., Rosenberg S. A., Sherwin S. A., Dinarello C. A., Longo D. L., Lane H. C. NIH conference. Immunomodulators in clinical medicine. Ann Intern Med. 1987 Mar;106(3):421–433. doi: 10.7326/0003-4819-106-3-421. [DOI] [PubMed] [Google Scholar]
  9. Fong S., Doyle M. V. Response of bovine and porcine peripheral blood mononuclear cells to human recombinant interleukin 2(125). Vet Immunol Immunopathol. 1986 Jan;11(1):91–100. doi: 10.1016/0165-2427(86)90091-7. [DOI] [PubMed] [Google Scholar]
  10. Good M. F., Pombo D., Lunde M. N., Maloy W. L., Halenbeck R., Koths K., Miller L. H., Berzofsky J. A. Recombinant human IL-2 overcomes genetic nonresponsiveness to malaria sporozoite peptides. Correlation of effect with biologic activity of IL-2. J Immunol. 1988 Aug 1;141(3):972–977. [PubMed] [Google Scholar]
  11. KISSLING R. E. Growth of rabies virus in non-nervous tissue culture. Proc Soc Exp Biol Med. 1958 Jun;98(2):223–225. doi: 10.3181/00379727-98-23997. [DOI] [PubMed] [Google Scholar]
  12. Katre N. V., Knauf M. J., Laird W. J. Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1487–1491. doi: 10.1073/pnas.84.6.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kawamura H., Rosenberg S. A., Berzofsky J. A. Immunization with antigen and interleukin 2 in vivo overcomes Ir gene low responsiveness. J Exp Med. 1985 Jul 1;162(1):381–386. doi: 10.1084/jem.162.1.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Larghi O. P., Nebel A. E. Rabies virus inactivation by binary ethylenimine: new method for inactivated vaccine production. J Clin Microbiol. 1980 Feb;11(2):120–122. doi: 10.1128/jcm.11.2.120-122.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Morgan D. A., Ruscetti F. W., Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007–1008. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
  17. Rosenberg S. A., Grimm E. A., McGrogan M., Doyle M., Kawasaki E., Koths K., Mark D. F. Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science. 1984 Mar 30;223(4643):1412–1414. doi: 10.1126/science.6367046. [DOI] [PubMed] [Google Scholar]
  18. Sehgal P. B., May L. T., Tamm I., Vilcek J. Human beta 2 interferon and B-cell differentiation factor BSF-2 are identical. Science. 1987 Feb 13;235(4790):731–732. doi: 10.1126/science.3492764. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Wang A., Lu S. D., Mark D. F. Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues. Science. 1984 Jun 29;224(4656):1431–1433. doi: 10.1126/science.6427925. [DOI] [PubMed] [Google Scholar]
  21. Weinberg A., Merigan T. C. Recombinant interleukin 2 as an adjuvant for vaccine-induced protection. Immunization of guinea pigs with herpes simplex virus subunit vaccines. J Immunol. 1988 Jan 1;140(1):294–299. [PubMed] [Google Scholar]
  22. West W. H., Tauer K. W., Yannelli J. R., Marshall G. D., Orr D. W., Thurman G. B., Oldham R. K. Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med. 1987 Apr 9;316(15):898–905. doi: 10.1056/NEJM198704093161502. [DOI] [PubMed] [Google Scholar]
  23. Wiktor T. J., György E., Schlumberger D., Sokol F., Koprowski H. Antigenic properties of rabies virus components. J Immunol. 1973 Jan;110(1):269–276. [PubMed] [Google Scholar]
  24. Wiktor T. J., Macfarlan R. I., Foggin C. M., Koprowski H. Antigenic analysis of rabies and Mokola virus from Zimbabwe using monoclonal antibodies. Dev Biol Stand. 1984;57:199–211. [PubMed] [Google Scholar]

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