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. 1980 Sep;29(3):966–971. doi: 10.1128/iai.29.3.966-971.1980

Further Studies of the Neuraminidase Content of Inactivated Influenza Vaccines and the Neuraminidase Antibody Responses After Vaccination of Immunologically Primed and Unprimed Populations

Alan P Kendal 1,2, F Marilyn Bozeman 2, Francis A Ennis 2
PMCID: PMC551225  PMID: 7429641

Abstract

Purified concentrates of influenza A/USSR/90/77(H1N1)-like, A/Texas/1/77 (H3N2)-like, and B/Hong Kong/5/72-like viruses used for preparation of investigational and licensed vaccines in 1978 to 1979 were tested for their content of neuraminidase enzyme activity. Concentrates of H1N1 virus used to prepare vaccines for clinical investigations performed in the spring of 1978 had neuraminidase activity at that time which decreased during storage to almost undetectable levels (three lots) or by 50% (one lot) by the winter of 1978. Several other lots of concentrates prepared with H1N1 virus and used for vaccine formulation had no detectable neuraminidase enzyme activity when tested in the winter of 1978, at a time when they would be administered in vaccines. The range of specific activity for different lots of concentrates was about 40-fold for A/Texas/1/77, B/Hong Kong/5/72, and A/USSR/90/77 neuraminidases. Immunogenicity of investigational vaccines prepared with tested concentrates and administered between April and July 1978 was measured in volunteers aged 13 to >50 years. Frequency of neuraminidase antibody rises to two doses of H1N1-containing vaccine was 10% in unprimed subjects aged <26 years and about 18 to 36% in older persons. The frequency of neuraminidase antibody rises to one dose of H3N2-containing vaccine varied from 0 to 32% in different groups (mean, 18%). The frequencies of neuraminidase antibody responses were always much lower than the frequencies of hemagglutinin antibody responses. These observations confirm the existence of practical difficulties in achieving uniformity of the neuraminidase content in influenza vaccines and of ensuring good immunogenicity of vaccine neuraminidase even in primed populations.

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Selected References

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

  1. Allan W. H., Madeley C. R., Kendal A. P. Studies with avian influenza A viruses: cross protection experiments in chickens. J Gen Virol. 1971 Aug;12(2):79–84. doi: 10.1099/0022-1317-12-2-79. [DOI] [PubMed] [Google Scholar]
  2. Beutner K. R., Chow T., Rubi E., Strussenberg J., Clement J., Ogra P. L. Evaluation of a neuraminidase-specific influenza A virus vaccine in children: antibody responses and effects on two successive outbreaks of natural infection. J Infect Dis. 1979 Dec;140(6):844–850. doi: 10.1093/infdis/140.6.844. [DOI] [PubMed] [Google Scholar]
  3. Brecht H., Hämmerling U., Rott R. Undisturbed release of influenza virus in the presence of univalent antineuraminidase antibodies. Virology. 1971 Nov;46(2):337–343. doi: 10.1016/0042-6822(71)90035-3. [DOI] [PubMed] [Google Scholar]
  4. Couch R. B., Kasel J. A., Gerin J. L., Schulman J. L., Kilbourne E. D. Induction of partial immunity to influenza by a neuraminidase-specific vaccine. J Infect Dis. 1974 Apr;129(4):411–420. doi: 10.1093/infdis/129.4.411. [DOI] [PubMed] [Google Scholar]
  5. Douglas R. G., Jr, Markoff L. J., Murphy B. R., Chanock R. M., Betts R. F., Hayden F. G., Levine M. M., Van Blerk G. A., Sotman S. B., Nalin D. R. Live Victoria/75-ts-1[E] influenza A virus vaccines in adult volunteers: role of hemagglutinin immunity in protection against illness and infection caused by influenza A virus. Infect Immun. 1979 Oct;26(1):274–279. doi: 10.1128/iai.26.1.274-279.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dowdle W. R., Coleman M. T., Mostow S. R., Kaye H. S., Schoenbaum S. C. Inactivated influenza vaccines. 2. Laboratory indices of protection. Postgrad Med J. 1973 Mar;49(569):159–163. doi: 10.1136/pgmj.49.569.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hennessy A. V., Minuse E., Davenport F. M. Antineuraminidase antibody response of man to influenza virus neuraminidase N2: results obtained with an improved hemagglutination inhibition technique and an enzyme inhibition test. J Immunol. 1972 Aug;109(2):213–216. [PubMed] [Google Scholar]
  8. Jahiel R. I., Kilbourne E. D. Reduction in plaque size and reduction in plaque number as differing indices of influenza virus-antibody reactions. J Bacteriol. 1966 Nov;92(5):1521–1534. doi: 10.1128/jb.92.5.1521-1534.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kendal A. P., Madeley C. R. Flocculation of influenza virus by specific anti-neuraminidase antibody. Arch Gesamte Virusforsch. 1970;31(3):219–229. doi: 10.1007/BF01253756. [DOI] [PubMed] [Google Scholar]
  10. Kendal A. P., Noble G. R., Dowdle W. R. Neuraminidase content of influenza vaccines and neuraminidase antibody responses after vaccination of immunologically primed and unprimed populations. J Infect Dis. 1977 Dec;136 (Suppl):S415–S424. doi: 10.1093/infdis/136.supplement_3.s415. [DOI] [PubMed] [Google Scholar]
  11. Kilbourne E. D. Comparative efficacy of neuraminidase-specific and conventional influenza virus vaccines in induction of antibody to neuraminidase in humans. J Infect Dis. 1976 Oct;134(4):384–394. doi: 10.1093/infdis/134.4.384. [DOI] [PubMed] [Google Scholar]
  12. Kilbourne E. D., Laver W. G., Schulman J. L., Webster R. G. Antiviral activity of antiserum specific for an influenza virus neuraminidase. J Virol. 1968 Apr;2(4):281–288. doi: 10.1128/jvi.2.4.281-288.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kim H. W., Arrobio J. O., Brandt C. D., Parrott R. H., Murphy B. R., Richman D. D., Chanock R. M. Temperature-sensitive mutants of influenza A virus: response of children to the influenza A/Hong Kong/68-ts-1(E) (H3N2) and influenza A/Udorn/72-ts-1(E) (H3N2) candidate vaccine viruses and significance of immunity to neuraminidase antigen. Pediatr Res. 1976 Apr;10(4):238–242. doi: 10.1203/00006450-197604000-00008. [DOI] [PubMed] [Google Scholar]
  14. Monto A. S., Kendal A. P. Effect of neuraminidase antibody on Hong Kong influenza. Lancet. 1973 Mar 24;1(7804):623–625. doi: 10.1016/s0140-6736(73)92196-x. [DOI] [PubMed] [Google Scholar]
  15. Murphy B. R., Kasel J. A., Chanock R. M. Association of serum anti-neuraminidase antibody with resistance to influenza in man. N Engl J Med. 1972 Jun 22;286(25):1329–1332. doi: 10.1056/NEJM197206222862502. [DOI] [PubMed] [Google Scholar]
  16. Murphy B. R., Markoff L. J., Hosier N. T., Rusten H. M., Chanock R. M., Kendal A. P., Douglas R. G., Betts R. F., Cate T. R., Jr, Couch R. B. Temperature-sensitive mutants of influenza A virus: evaluation of A/Victoria/3/75-ts-1[E] recombinant viruses in volunteers. Infect Immun. 1978 Jun;20(3):671–677. doi: 10.1128/iai.20.3.671-677.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Noble G. R., Kaye H. S., Yarbrough W. B., Fiedler B. K., Reed C. J., Felker M. B., Kendal A. P., Dowdle W. R. Measurement of hemagglutination-inhibiting antibody to influenza virus in the 1976 influenza vaccine program: methods and test reproducibility. J Infect Dis. 1977 Dec;136 (Suppl):S429–S434. doi: 10.1093/infdis/136.supplement_3.s429. [DOI] [PubMed] [Google Scholar]
  18. Ogra P. L., Chow T., Beutner K. R., Rubi E., Strussenberg J., DeMello S., Rizzone C. Clinical and immunologic evaluation of neuraminidase-specific influenza A virus vaccine in humans. J Infect Dis. 1977 Apr;135(4):499–506. doi: 10.1093/infdis/135.4.499. [DOI] [PubMed] [Google Scholar]
  19. Schulman J. L., Khakpour M., Kilbourne E. D. Protective effects of specific immunity to viral neuraminidase on influenza virus infection of mice. J Virol. 1968 Aug;2(8):778–786. doi: 10.1128/jvi.2.8.778-786.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Virelizier J. L. Host defenses against influenza virus: the role of anti-hemagglutinin antibody. J Immunol. 1975 Aug;115(2):434–439. [PubMed] [Google Scholar]
  21. Webster R. G., Laver W. G. Preparation and properties of antibody directed specifically against the neuraminidase of influenza virus. J Immunol. 1967 Jul;99(1):49–55. [PubMed] [Google Scholar]
  22. Wood J. M., Schild G. C., Newman R. W., Seagroatt V. An improved single-radial-immunodiffusion technique for the assay of influenza haemagglutinin antigen: application for potency determinations of inactivated whole virus and subunit vaccines. J Biol Stand. 1977;5(3):237–247. doi: 10.1016/s0092-1157(77)80008-5. [DOI] [PubMed] [Google Scholar]

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