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Inactivated smallpox vaccine. A comparison of inactivation methods

Published online by Cambridge University Press:  15 May 2009

G. S. Turner
Affiliation:
The Lister Institute of Preventive Medicine, Elstree, Hertfordshire
E. J. Squires
Affiliation:
The Lister Institute of Preventive Medicine, Elstree, Hertfordshire
H. G. S. Murray
Affiliation:
The Lister Institute of Preventive Medicine, Elstree, Hertfordshire
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Vaccines were prepared from a single pool of high-titred vaccinia virus and inactivated by six methods, namely heat, formalin, hydroxylamine, β-propiolactone, ultraviolet irradiation, and visible light and methylene blue. Large doses of the vaccines were required to protect mice against intracerebral challenge. Differences in protection were not attributable to the method of their inactivation. The vaccines also induced similar degrees of skin immunity in rabbits which showed no severe dermal reactions when challenged with either homologous killed vaccine or live virus. The virus-neutralizing, haemagglutinin-inhibiting and complement fixing antibody responses to the vaccines differed; heat-inactivation preserved these antigens least well and β-propiolactone apparently the best. In both rabbits and mice there was little association between the different antibody responses to each vaccine or between the degrees of antibody response and the protection they induced. The relation of these findings to pox-virus immunity and the use of inactivated smallpox vaccine in man is discussed.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1970

References

REFERENCES

Abel, P. (1963). Reactivation of heated vaccinia virus in vitro. Zeitschrift für Vererbungslehre 94, 249.Google ScholarPubMed
Allison, A. C. (1967). Cell-mediated immune responses to virus infections and virus induced tumours. British Medical Bulletin 23, 60.CrossRefGoogle ScholarPubMed
Amies, C. (1961). Loss of immunogenic properties of vaccinia virus inactivated by formaldehyde. Canadian Journal of Microbiology 7, 141.CrossRefGoogle ScholarPubMed
Andrewes, C. H., Elford, W. J. & Niven, J. S. F. (1948). Vaccinia and ectromelia in the mouse. British Journal of Experimental Pathology 29, 329.Google ScholarPubMed
Baron, S., Buckler, C. E., Friedman, R. M. & McCloskey, R. V. (1966). Role of interferon during viremia. II. Protective action of circulating interferon. Journal of Immunology 96, 17.CrossRefGoogle ScholarPubMed
Beunders, B. W. J., Driessen, J. H. & van den Hoek, C. (1960). Clinical picture and serological response to vaccination with formalinized vaccinia virus followed by scarification with active vaccine in military personnel. Archiv für die gesamte Virusforschung 10, 382.CrossRefGoogle Scholar
Boulter, E. A. (1969). Protection against poxviruses. Proceedings of the Royal Society of Medicine 62, 295.CrossRefGoogle ScholarPubMed
Boulter, E. A., Zwartouw, H. T. & Titmuss, D. H. (1964). The immunization of rabbits with inactivated vaccinia virus. Journal of General Microbiology 37, iv.Google Scholar
Briody, B. A. (1959). Response of mice to ectromelia and vaccinia viruses. Bacteriological Reviews 23, 61.CrossRefGoogle ScholarPubMed
Bronson, L. H. & Parker, R. F. (1944). Vaccinial infection in the mouse. Journal of Immunology 49, 193.CrossRefGoogle Scholar
Collier, L. H., McClean, D. & Vallet, L. (1955). The antigenicity of ultraviolet irradiated vaccinia virus. Journal of Hygiene 53, 513.Google Scholar
Craigie, J. & Wishart, F. O. (1933). Skin sensitivity to the elementary bodies of vaccinia. Candian Journal of Public Health 24, 72.Google Scholar
Donally, H. H. & Weil, A. J. (1940). Formalised vaccinia virus. Results of its use with children who had never been vaccinated previously. Journal of Pediatrics 17, 639.Google Scholar
Dostal, V. (1962). Problems related to the inactivation of vaccinia virus. In Symposium International sur la Vaccination Antivariolique,Lyon 7–8 Dec. 1962.Lyon: Merieux.Google Scholar
Ehrengut, W. (1968). Impfreaktionen und Pockenimpfschutz. Deutsche medizinische Wochenschrift 93, 948.CrossRefGoogle Scholar
Ehrengut, W. (1969). Non-infectious smallpox vaccines. In: Symposium on Smallpox.Zagreb 2–3 September 1969.Google Scholar
Epp, C. Von (1961). Uber das Antikörperbild des Menschen bei normalem und gestortem Verlauf einer Pockenschutzimpfung. Archiv für Hygiene und Bakteriologie 145, 256.Google Scholar
Fellowes, O. N. (1966). Hydroxylamine as an inactivating agent for foot-and-mouth disease virus. Journal of Immunology 96, 772.CrossRefGoogle ScholarPubMed
Fenner, F. (1962). The reactivation of animal viruses. British Medical Journal ii, 135.CrossRefGoogle Scholar
Finter, N. B. (1966). Interferons. In Frontiers of Biology 2. Amsterdam: North Holland Pub. Co.Google Scholar
Franklin, R. M. & Wecker, E. (1959). Inactivation of some animal viruses by hydroxylamine and the structure of ribonucleic acid. Nature, London 184, 383.CrossRefGoogle ScholarPubMed
Freese, E., Bautz-Freese, E. & Bautz, E. (1961). Hydroxylamine as a mutagenic and inactivating agent. Journal of Molecular Biology 3, 133.CrossRefGoogle ScholarPubMed
Friedberger, E. & Yamamoto, J. (1909). Zur Desinfektion und experimentellen Therapie bei Vaccine. Zentralblatt f¨r Bakteriologie, Parasitenkunde und Infektionskrankheiten Abt. 1, Ref. 44 (suppl.), 81.Google Scholar
Gard, S. (1957). In The Nature of Viruses, p. 121. Ed. Wolstenholme, G. E. W. and Millar, E. C. P., London: J. & A. Churchill Ltd.Google Scholar
Gard, S. (1960). Theoretical considerations in the inactivation of viruses by chemical means. Annals of the New York Academy of Sciences 83, 638.CrossRefGoogle ScholarPubMed
Gifford, G. E. (1963). Studies on the specificity of Interferon. Estimation of mouse interferon. Journal of General Microbiology 33, 437.CrossRefGoogle Scholar
Herrlich, A. (1959). Über Vakzine Antigen, Versuche einer Prophylaxe neuraler Impfschaden. Münchener medizinishe Wochenschrift 101, 12.Google Scholar
Hirsch, M. S., Nahmias, A. J., Murphy, F. A. & Kramer, J. H. (1968). Cellular immunity in vaccinia infection of mice. Antithymocyte serum effects on primary and secondary responsiveness. Journal of Experimental Medicine 128, 121.CrossRefGoogle ScholarPubMed
Hochstein-Mintzel, V. (1969). Passive und adoptive Immunisierung der Säuglingsmaus gegen Poxvirus vaccinae und variolae. Bin Beitrag zur Wertigkeitsprüfung von Pocken-impstoffen. Zeitschrift für Immunitätsforschung und experimentelle Therapie 138, 71.Google Scholar
Janson, C. (1891). Versuche zur Erlangung künstlicher Immunität bei Variola vaccina. Zentralblatt für Bakteriologie und Parasitenkunde 10, 40.Google Scholar
Kaplan, C. (1962). A non-infectious smallpox vaccine. Lancet ii, 1027.CrossRefGoogle Scholar
Kaplan, C., Benson, P. F. & Butler, N. R. (1965). Immunogenieity of ultraviolet-irradiated non-infectious vaccinia virus-vaccine in infants and young children. Lancet i, 573.CrossRefGoogle Scholar
Kaplan, C., McClean, D. & Vallet, L. (1962). A note on the immunogenicity of ultraviolet irradiated vaccinia-virus in man. Journal of Hygiene 60, 79.CrossRefGoogle ScholarPubMed
Kempe, C. H., Bowles, C., Meiklejohn, G., Berge, T. O., St Vincent, L., Sundara, Babu B. V., Govindarajan, S., Ratnakannan, N. R., Downie, A. W. & Murthy, V. R. (1961). The use of vaccinia hyperimmune gamma-globulin in the prophylaxis of smallpox. Bulletin of the World Health Organization 25, 41.Google ScholarPubMed
Kim, K. S. & Sharp, D. G. (1967). Influence of the physical state of formalinised vaccinia virus particles on surviving plaque titre: Evidence for multiplicity reactivation. Journal of Immunology 99, 1221.CrossRefGoogle Scholar
Kimes, R. C. & Bussell, R. H. (1968). Nucleic acid type and effect of pH and hydroxylamine on canine distemper virus. Archiv für die gesamte Virusforschung 24, 387.CrossRefGoogle ScholarPubMed
Lindenman, J. Von & Buser, F. (1962). Das inaktivierte Vakzine-Antigen nach Herrlich: Versuch einer serologischen Antigenitätsprüfung am Menschen. Pathologia et Microbiologia 25, 478.Google Scholar
Lo Grippo, G. A. (1960). Investigations of the use of β-propiolactone in virus inactivation. Annals of the New York Academy of Sciences 83, 578.CrossRefGoogle Scholar
McCarthy, K. & Helbert, D. (1960). A comparison of the haemagglutinins of variola, alastrim, vaccinia, cowpox and ectromelia viruses. Journal of Pathology and Bacteriology, 79, 416.CrossRefGoogle Scholar
McNeill, T. A. (1965). The antibody response of rabbits to inactivated vaccinia virus. Journal of Hygiene 63, 525.Google ScholarPubMed
McNeill, T. A. (1966). The development of skin resistance and hypersensitivity following inactivated virus vaccines in rabbits. Journal of Hygiene 64, 23.CrossRefGoogle ScholarPubMed
Madeley, C. R. (1968). The immunogenicity of heat-inactivated vaccinia virus in rabbits. Journal of Hygiene 66, 89.CrossRefGoogle ScholarPubMed
Mahnel, H. (1960). Tierexperimentelle Untersuchungen mit Vakzine-Antigen. Archiv für die gesamte Virusforschung 10, 529.CrossRefGoogle Scholar
Mannweiler, E. & Geister, R. (1967). Das Verhalten der Serurnantikörper bei Wiederimpfung mit Vakzinevirus. Deutsche medizinische Wochenschrift 92, 2168.CrossRefGoogle Scholar
Parker, R. F. & Rivers, T. M. (1936). Immunological and chemical investigations of vaccine virus. III. Response of rabbits to inactive elementary bodies of vaccinia and to virus-free extracts of vaccinia virus. Journal of Experimental Medicine 63, 69.CrossRefGoogle Scholar
Ramano, Rao A. V. (1962). The immunogenicity of inactivated vaccinia virus. Journal of Pathology and Bacteriology 84, 367.CrossRefGoogle Scholar
Rohde, W. (1968). Versuch einer Gegenuberstellung bisheriger Unterlagen einer Einschätzung der Enzephalitis-prophylaxe mittels Vakzineantigen in der D.D.R. Zeitschrift für ärtzliche Fortbildung 62, 177.Google Scholar
Rondle, C. J. M. & Dumbell, K. R. (1962). Antigens of cowpox virus. Journal of Hygiene 60, 41.CrossRefGoogle ScholarPubMed
Rosenau, M. J. & Andervont, H. B. (1931). Vaccinia: susceptibility of mice and immunologic studies. American Journal of Hygiene 13, 728.Google Scholar
Schäfer, W. & Rott, R. (1962). Herstellung von Virus Vaccinen mit Hydroxylamine; verlauf das Inaktivierung und Wirkung des Hydroxylamins auf verschiedene biologische Eigenschaften einiger Viren. Zeitschrift für Hygiene und Infektionskrankheiten 148, 256.CrossRefGoogle Scholar
Seligmann, E. B. Jr (1966). World Health Organization Monograph Series No. 23, p. 146.Google Scholar
Sitnikov, B. S. & Ghendon, Yu Z. (1968). Resistance of variola-vaccinia subgroup of viruses to treatments predominantly damaging the protein envelope or the nucleic component of the virus. Voprosy Virusologii 13, 554.Google ScholarPubMed
Subrahmanyan, T. P. & Mims, C. A. (1966). Fate of intravenously administered interferon and the distribution of interferon during virus infections of mice. British Journal of Experimental Pathology 47, 168.Google Scholar
Taylor, A. R. (1960). Effects of non-ionizing radiations on animal viruses. Annals of the New York Academy of Sciences 83, 670.CrossRefGoogle ScholarPubMed
Turner, G. S. (1967). Respiratory infection of mice with vaccinia virus. Journal of General Virology 1, 399.CrossRefGoogle ScholarPubMed
Turner, G. S. & Kaplan, C. (1965). Observations on photodynamic inactivation of vaccinia virus and its effect on immunogenicity. Journal of Hygiene 63, 395.CrossRefGoogle ScholarPubMed
Wallis, C. & Melnick, J. L. (1965). Photodynamic inactivation of animal viruses: A Review. Photochemistry & Photobiology 4, 159.CrossRefGoogle Scholar
Weil, A. J. & Gall, L. S. (1940). Studies on the immunization of rabbits with formalinized vaccine virus. Journal of Immunology 38, 1.CrossRefGoogle Scholar
Woese, C. (1960). Thermal inactivation of animal viruses. Annals of the New York Academy of Sciences 83, 741.CrossRefGoogle ScholarPubMed