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. 1977 Feb;15(2):347–353. doi: 10.1128/iai.15.2.347-353.1977

Selection of influenza B virus recombinants and their testing in humans for attenuation and immunogenicity.

A S Beare, J E Sherwood, K A Callow, J W Craig
PMCID: PMC421373  PMID: 844900

Abstract

The selection of influenza B virus recombinants from plaques in bovine kidney cell monolayers is described. Two sets of recombinants were each derived from parents of high and low virulence for humans, respectively. Recombination frequency was apparently high, and reassortment of genes made it possible to obtain attenuated recombinants containing the surface antigens of the virulent parents. Attenuation and immunogenicity were demonstrated in a series of volunteer trials. However, technique proved less satisfactory than for influenza A viruses which periodically undergo antigenic shift and for which there is a wide choice of parent viruses with distinctive surface antigens. In our two influenza B recombinant series there was appreciable antigenic overlap in the neuraminidases of the parents, even though in both cases these were chronologically widely separated. Another marker used was comparative titer at 35 and 38 degrees C. In practice, technical problems might sometimes make it difficult to ensure rapid production of live influenza B vaccines by recombination.

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Selected References

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  1. Appleyard G., Maber H. B. Plaque formation by influenza viruses in the presence of trypsin. J Gen Virol. 1974 Dec;25(3):351–357. doi: 10.1099/0022-1317-25-3-351. [DOI] [PubMed] [Google Scholar]
  2. BURNET F. M. A genetic approach to variation in influenza viruses; variation in the strain NWS on allantoic passage. J Gen Microbiol. 1951 Feb;5(1):54–58. doi: 10.1099/00221287-5-1-54. [DOI] [PubMed] [Google Scholar]
  3. BURNET F. M., LIND P. E. A genetic approach to variation in influenza viruses; recombination of characters between the influenza virus A strain NWS and strains of different serological subtypes. J Gen Microbiol. 1951 Feb;5(1):67–82. doi: 10.1099/00221287-5-1-67. [DOI] [PubMed] [Google Scholar]
  4. BURNET F. M., LIND P. E. A genetic approach to variation in influenza viruses; recombination of characters in influenza virus strains used in mixed infections. J Gen Microbiol. 1951 Feb;5(1):59–66. doi: 10.1099/00221287-5-1-59. [DOI] [PubMed] [Google Scholar]
  5. Beare A. S., Bynoe M. L., Tyrrell D. A. Investigetion into the attenuation of influenza viruses by serial passage. Br Med J. 1968 Nov 23;4(5629):482–484. doi: 10.1136/bmj.4.5629.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beare A. S., Hall T. S. Recombinant influenza-A viruses as live vaccines for man. Report to the Medical Research Council's Committee on Influenza and other Respiratory Virus Vaccines. Lancet. 1971 Dec 11;2(7737):1271–1273. doi: 10.1016/s0140-6736(71)90597-6. [DOI] [PubMed] [Google Scholar]
  7. Beare A. S., Keast K. A. Influenza virus plaque formation in different species of cell monolayers. J Gen Virol. 1974 Mar;22(3):347–354. doi: 10.1099/0022-1317-22-3-347. [DOI] [PubMed] [Google Scholar]
  8. Beare A. S., Keast K. Plaque formation by influenza B viruses in primary calf kidney cell monolayes. J Gen Virol. 1971 Nov;13(2):321–325. doi: 10.1099/0022-1317-13-2-321. [DOI] [PubMed] [Google Scholar]
  9. Callow K. A., Beare A. S. Measurement of antibody to influenza virus neuraminidase by single radial hemolysis in agarose gels. Infect Immun. 1976 Jan;13(1):1–8. doi: 10.1128/iai.13.1.1-8.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chakraverty P. Antigenic relationship between influenza B viruses. Bull World Health Organ. 1971;45(6):755–766. [PMC free article] [PubMed] [Google Scholar]
  11. Chakraverty P. Antigenic relationships between the neuraminidases of influenza B virus. Bull World Health Organ. 1972;46(4):473–476. [PMC free article] [PubMed] [Google Scholar]
  12. GOTLIEB T., HIRST G. K. The experimental production of combination forms of virus. III. The formation of doubly antigenic particles from influenza A and B virus and a study of the ability of individual particles of X virus to yield two separate strains. J Exp Med. 1954 Apr 1;99(4):307–320. doi: 10.1084/jem.99.4.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kilbourne E. D. Future influenza vaccines and the use of genetic recombinants. Bull World Health Organ. 1969;41(3):643–645. [PMC free article] [PubMed] [Google Scholar]
  14. Klenk H. D., Rott R., Orlich M., Blödorn J. Activation of influenza A viruses by trypsin treatment. Virology. 1975 Dec;68(2):426–439. doi: 10.1016/0042-6822(75)90284-6. [DOI] [PubMed] [Google Scholar]
  15. LEIBOVITZ A. THE GROWTH AND MAINTENANCE OF TISSUE-CELL CULTURES IN FREE GAS EXCHANGE WITH THE ATMOSPHERE. Am J Hyg. 1963 Sep;78:173–180. doi: 10.1093/oxfordjournals.aje.a120336. [DOI] [PubMed] [Google Scholar]
  16. Laver W. G., Kilbourne E. D. Identification in a recombinant influenza virus of structural proteins derived from both parents. Virology. 1966 Nov;30(3):493–501. doi: 10.1016/0042-6822(66)90125-5. [DOI] [PubMed] [Google Scholar]
  17. Lazarowitz S. G., Choppin P. W. Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide. Virology. 1975 Dec;68(2):440–454. doi: 10.1016/0042-6822(75)90285-8. [DOI] [PubMed] [Google Scholar]
  18. McCahon D., Schild G. C. Segregation of antigenic and biological characteristics during influenza virus recombination. J Gen Virol. 1972 Apr;15(1):73–77. doi: 10.1099/0022-1317-15-1-73. [DOI] [PubMed] [Google Scholar]
  19. Murphy B. R., Chalhub E. G., Nusinoff S. R., Chanock R. M. Temperature-sensitive mutants of influenza virus. II. Attenuation of ts recombinants for man. J Infect Dis. 1972 Aug;126(2):170–178. doi: 10.1093/infdis/126.2.170. [DOI] [PubMed] [Google Scholar]
  20. Okuno Y., Nakamura K. Prophylactic effectiveness of live influenza vaccine in 1965. Biken J. 1966 Jun;9(2):89–95. [PubMed] [Google Scholar]
  21. PERRY B., BURNET F. M. Recombination studies with two influenza virus B strains. Aust J Exp Biol Med Sci. 1953 Oct;31(5):519–528. doi: 10.1038/icb.1953.55. [DOI] [PubMed] [Google Scholar]
  22. SIMPSON R. W., HIRST G. K. Genetic recombination among influenza viruses. I. Cross reactivation of plaque-forming capacity as a method for selecting recombinants from the progeny of crosses between influenza A strains. Virology. 1961 Dec;15:436–451. doi: 10.1016/0042-6822(61)90111-8. [DOI] [PubMed] [Google Scholar]
  23. Schulman J. L., Kilbourne E. D. Independent variation in nature of hemagglutinin and neuraminidase antigens of influenza virus: distinctiveness of hemagglutinin antigen of Hong Kong-68 virus. Proc Natl Acad Sci U S A. 1969 Jun;63(2):326–333. doi: 10.1073/pnas.63.2.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Siekmann U., Schoop H. J., Kuwert E. Contribution to the standardization of influenza neuraminidase inhibition tests, based on enzyme- antienzyme kinetic studies. Dev Biol Stand. 1975;28:324–335. [PubMed] [Google Scholar]
  25. Spencer M. J., Cherry J. D., Powell K. R., Sumaya C. V., Garakian A. J. Clinical trials with Alice strain, live, attenuated, serum inhibitor-resistant intranasal influenza A vaccine. J Infect Dis. 1975 Oct;132(4):415–420. doi: 10.1093/infdis/132.4.415. [DOI] [PubMed] [Google Scholar]
  26. Tobita K., Kilbourne E. D. Genetic recombination for antigenic markers of antigenically different strains of influenza B virus. J Virol. 1974 Feb;13(2):347–352. doi: 10.1128/jvi.13.2.347-352.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]

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