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. 2002 Nov 12;8(4):299–303. doi: 10.1016/0264-410X(90)90083-X

Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine

Hans G Bahnemann 1
PMCID: PMC7173316  PMID: 2204242

Abstract

Viral antigens for human and veterinary vaccines are still inactivated with formaldehyde. This is not an ideal inactivant and the problems of formaldehyde inactivation of vaccines are discussed. Vaccines inactivated with aziridines are superior in safety and antigenicity. Aziridines inactivate viruses in a first-order reaction and the inactivation rate and endpoint can be determined. The preparation and application of the aziridine compound binary ethylenimine (BEI) and the necessary conditions for and controls of the inactivation process are described and discussed. A computer program has been written for assistance in the use of BEI for controlled inactivation of viral antigens.

Keywords: Inactivation, binary ethylenimine, viral antigens

References

  • 1.Wesslén T., Lycke E., Gard S., Olin G. Inactivation of poliomyelitis virus by formaldehyde. Arch. Ges. Virusf. 1957;7:125–135. doi: 10.1007/BF01241813. [DOI] [PubMed] [Google Scholar]
  • 2.Gard S., Lycke E. Analysis of inactivation curves. Vol. 7. 1957. Inactivation of poliovirus by formaldehyde; pp. 471–493. (Arch. Ges. Virusf.). [DOI] [PubMed] [Google Scholar]
  • 3.Wesslén T., Dinter Z. The inactivation of foot-and-mouth disease virus by formalin. Arch. Ges. Virusf. 1957;7:394–401. doi: 10.1007/BF01240747. [DOI] [PubMed] [Google Scholar]
  • 4.Graves J.H. Formaldehyde inactivation of foot-and-mouth disease virus as applied to vaccine preparation. Am. J. Vet. Res. 1963;24:1131–1135. [PubMed] [Google Scholar]
  • 5.Barteling S.J., Woortmeyer R. Conditions for the preparation of safe vaccine. Vol. 80. 1984. Formaldehyde inactivation of foot-and-mouth disease virus; pp. 103–117. (Arch. Virol.). [DOI] [PubMed] [Google Scholar]
  • 6.Schultz P., Rightsel W.A., Timm E.A., Taylor A.R., McLean I.W., Jr. Partially inactivated poliomyelitis virus: initiation of infection in tissue culture. J. Immunol. 1957;79:497–507. [PubMed] [Google Scholar]
  • 7.Böttiger M., Lycke E., Mélen B., Wrange G. Incubation time in tissue culture of formalin treated virus. Vol. 8. 1958. Inactivation of poliomyelitis virus by formaldehyde; pp. 259–266. (Arch. Ges. Virusf.). [PubMed] [Google Scholar]
  • 8.Polatnick J., Arlinghaus R., Graves J.H., Cowan K.M. Inhibition of cell-free foot-and-mouth disease virus ribonucleic acid synthesis by antibody. Virology. 1967;31:609–615. doi: 10.1016/0042-6822(67)90189-4. [DOI] [PubMed] [Google Scholar]
  • 9.Alonso A., de Mello P.A., Gomes I., Rosenberg F. The use of virus-infection-associated antigen (VIA) in the detection of cattle exposed to foot-and-mouth disease. Bull. C.P.F.A. 1975:17–18. [Google Scholar]; Alonso A., de Mello P.A., Gomes I., Rosenberg F. The use ov virus-infection-associated antigen (VIA) in the detection of cattle exposed to foot-and-mouth disease. Bull. C.P.F.A. 1975:17–24. [Google Scholar]
  • 10.Pinto A.A., Garland A.J.M. Immune response to virus-infection-associated (VIA) antigen in cattle repeatedly vaccinated with foot-and-mouth disease virus inactivated by formalin or acetylethylenimine. J. Hyg. Camb. 1979;82:41–50. doi: 10.1017/s0022172400025456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Alonso A., Gomes I., Bahnemann H.G. The induction of antibodies against VIAA in cattle vaccinated and revaccinated with inactivated FMD vaccine. Bull. C.P.F.A. 1988;54:53–54. in press. [Google Scholar]
  • 12.Lucam F., Mackowiak C., Magat A. La vaccination anti-aphteuse en France. Bull. O.I.E. 1958;49:230–256. [Google Scholar]
  • 13.Beck E., Strohmaier K. Subtyping of European foot-and-mouth disease strains by nucleotide sequence determination. J. Virol. 1987;61:1621–1629. doi: 10.1128/jvi.61.5.1621-1629.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Strohmaier K. III. Erfahrungen und Folgerungen aus 20 Jahren Bekämpfung der Maul- und Klauenseuche. Vol. 42. 1987. Die Maul-und Klauenseuche; pp. 417–422. (Tierärztl. Umschau). [Google Scholar]
  • 15.Raettig H., Uecker W. Inaktivierung von Bakteriophagen durch Äthyleniminderivate. Naturwissensch. 1955;42:490. [Google Scholar]
  • 16.Hurst A. Approaches to the chemotherapy of virus diseases. J. Pharm. Pharmacol. 1957;9:273–292. doi: 10.1111/j.2042-7158.1957.tb12281.x. [DOI] [PubMed] [Google Scholar]
  • 17.Girard H.C.C., Bayramoglu O., Erol N., Burgut A. Inactivation of O1 FMD virus by binary ethylenimine (BEI) Bull. O.I.E. 1977;87:201–217. [Google Scholar]
  • 18.Makarasen P., Sinsuwonkwat P., Tanachareonwatch P. Veterinary Viral Diseases: Their Significance in South-East Asia and the Western Pacific. Academic Press; Australia: 1985. Binary ethylenimine and foot-and-mouth disease vaccine production in Thailand; pp. 308–309. [Google Scholar]
  • 19.Buonavoglia C., Fioretti A., Tollis M., Menna F., Papparella V. A preliminary vaccine potency trial of a Newcastle disease virus inactivated with binary ethylenimine. Vet. Res. Comm. 1988;12:195–197. doi: 10.1007/BF00362801. [DOI] [PubMed] [Google Scholar]
  • 20.ICI: Br. Pat. 806 949 and 806 950 (1959)
  • 21.Brown F., Crick J. Application of agar-gel diffusion analysis to a study of the antigenic structure of inactivated vaccines prepared from the virus of foot-and-mouth disease. J. Immunol. 1959;82:444–447. [PubMed] [Google Scholar]
  • 22.Uecker W. I. Untersuchungen zur Kinetik der Inaktivierung von Bakteriophagen. Vol. 181. 1961. Inaktivierung von Mikroorganismen durch Alkylierende Verbindungen; pp. 516–531. (Zentralbl. Bakteriol Hyg. Abt. I. Orig.). [Google Scholar]
  • 23.Graves J.H., Arlinghaus R.B. Proc. 71st Ann. Meeting US Livest. Sanit. Assoc. 1967. Acetylethylenimine in the preparation of inactivated foot-and-mouth disease vaccines; pp. 396–403. [PubMed] [Google Scholar]
  • 24.Fellowes O.N. Comparison of the inactivation and antigenicity of foot-and-mouth disease virus by acetylethylenimine and by combined effect of ultraviolet light and β-propiolactone. J. Immunol. 1965;95:1100–1106. [PubMed] [Google Scholar]
  • 25.Pay T.W.F. Some observations on foot-and-mouth disease virus inactivation with acetylethylenimine. Meeting Technical Committee; Tübingen; Rome: FAO; 1971. [Google Scholar]
  • 26.Pay T.W.F., Telling R.C., Thorne A.C. Inactivation of FMD virus with aziridines. Meeting Technical Committee; Tübingen; Rome: FAO; 1981. [Google Scholar]
  • 27.Bahnemann H.G. The inactivation of foot-and-mouth disease virus by ethylenimine and propylenimine. Zentralbl. Vet. Med. B. 1973;20:356–360. doi: 10.1111/j.1439-0450.1973.tb01136.x. [DOI] [PubMed] [Google Scholar]
  • 28.Bahnemann H.G., Mesquita J., Astudillo V., Dora F. The production and application of an oil adjuvant vaccine against foot-and-mouth disease in cattle. In: Spier R.E., Griffiths J.B., editors. Modern Approaches to Animal Cell Technology. Butterworth & Co; UK: 1987. [Google Scholar]
  • 29.Bauer K. Die Inaktivierung des Maul-und Klauenseuche (MKS) Virus durch Äthyläthylenimine und die Eignung des inaktivierten Virus zur Impfstoffherstellung. Zentralbl. Bakteriol. Hyg. Abt. I Orig. 1970;213:285–297. [PubMed] [Google Scholar]
  • 30.Bahnemann H.G. Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production. Arch. Virol. 1975;47:47–56. doi: 10.1007/BF01315592. [DOI] [PubMed] [Google Scholar]
  • 31.Schloer G.M. Vol. 86. 1982. Kinetics of inactivation of African swine fever antigen with binary ethylenimine; pp. 253–260. (Proc. US Anim. Health Assoc.). [Google Scholar]
  • 32.Barber T.L., Jochim M.M. 1978. Inactivation of bluetongue virus with binary ethylenimine; p. 339. (Ann. Meet. Am. Soc. Microbiol.). [Google Scholar]
  • 33.Miller J.M., Van der Maaten M.J. Evaluation of an inactivated bovine leukemia virus preparation as an immunogen in cattle. Ann. Rech. Vet. 1978;9:871–877. [PubMed] [Google Scholar]
  • 34.Bahnemann H.G. Inactivation of viruses in serum with binary ethylenimine. J. Clin. Microbiol. 1976;3:209–210. doi: 10.1128/jcm.3.2.209-210.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Crouch C.F. Vaccination against enteric rota and coronaviruses in cattle and pigs: enhancement of lactogenic immunity. Vaccine. 1985;3:284–291. doi: 10.1016/S0264-410X(85)90056-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Heuschele W.P. Inactivation of adventitious viruses in serum. Art to Science. 1984;3:2. [Google Scholar]
  • 37.Wrathall A.E., Wells D.E., Cartwright S.F., Frerichs G.N. An inactivated oil emulsion vaccine for the prevention of porcine parvovirus-induced reproductive failure. Res. Vet. Sci. 1984;36:136–143. [PubMed] [Google Scholar]
  • 38.Sun I.L., Gustafson D.P., Scherba G. Comparison of pseudorabies virus inactivated by bromo-ethylenimine, 60Co irradiation and acridine dye in immune assay systems. J. Clin. Microbiol. 1978;8:604–611. doi: 10.1128/jcm.8.5.604-611.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Larghi O.P., Nebel A.E. Rabies virus inactivation by binary ethylenimine: new method for inactivated vaccine production. J. Clin. Microbiol. 1980;11:120–122. doi: 10.1128/jcm.11.2.120-122.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Lycke E. The effect upon the rate of inactivation of temperature, pH and concentration of formaldehyde. Vol. 8. 1958. Studies of the inactivation of poliomyelitis virus by formaldehyde; pp. 267–284. (Arch. Ges. Virusf.). [DOI] [PubMed] [Google Scholar]
  • 41.Epstein J., Rosenthal R.W., Ess R.J. Use of γ-(4-nitrobenzyl)-pyridine as analytical reagent for ethylenimines and other alkylating agents. Anal. Chem. 1955;27:1435–1439. [Google Scholar]
  • 42.Czelleng F., Farkas L., Perenyi T., Fazekas A., Szalai F., Zsitvai K., Erdelyi K. Effect of ethylenimine and formaldehyde inactivation on the immunogenicity of foot-and-mouth disease virus. XVth Conf. O.I.E. Commission on Foot-and-Mouth Disease; Paris; 10–14 October 1978. [Google Scholar]
  • 43.Preaud J., Dubourget P., Detraz N., Lombard M. Inactivation of Foot-and-Mouth Disease Virus by Ethylenimine — Kinetics and Control. Int. Foot-and-Mouth Disease Symp. Ankara; Turkey; Ankara: FMD Institute; June 1989. [Google Scholar]
  • 44.Dermer O.C., Ham G.E. Academic Press; New York: 1969. p. 400. (Ethylenimine and other Aziridines). [Google Scholar]

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