Location of Repository

Selection of neutralizing antibody escape mutants with type A influenza virus HA-specific polyclonal antisera: possible significance for antigenic drift

By S. Matthew Cleveland, H. P. Taylor and N. J. Dimmock

Abstract

Ten antisera were produced in rabbits by two or three intravenous injections of inactivated whole influenza type A virions. All contained haemagglutination-inhibition (HI) antibody directed predominantly to an epitope in antigenic site B and, in addition, various amounts of antibodies to an epitope in site A and in site D. The ability of untreated antisera to select neutralization escape mutants was investigated by incubating virus possessing the homologous haemagglutinin with antiserum adjusted to contain anti-B epitope HI titres of 100, 1000 and 10000 HIU/ml. Virus-antiserum mixtures were inoculated into embryonated hen's eggs, and progeny virus examined without further selection. Forty percent of the antisera at a titre of 1000 HIU/ml selected neutralizing antibody escape mutants as defined by their lack of reactivity to Mab HC10 (site B), and unchanged reactivity to other Mabs to site A and site D epitopes. All escape mutant-selecting antisera had a ratio of anti-site B (HC10)-epitope antibody[ratio]other antibodies of [gt-or-equal, slanted]2·0[ratio]1. The antiserum with the highest ratio (7·4[ratio]1) selected escape mutants in all eggs tested in four different experiments. No antiserum used at a titre of 10000 HIU/ml allowed multiplication of any virus. All antisera used at a titre of 100 HIU/ml permitted virus growth, but this was wild-type (wt) virus. We conclude that a predominant epitope-specific antibody response, a titre of [gt-or-equal, slanted]1000 HIU/ml, and a low absolute titre of other antibodies ([less-than-or-eq, slant]500 HIU/ml) are three requirements for the selection of escape mutants. None of the antisera in this study could have selected escape mutants without an appropriate dilution factor, so the occurrence of an escape mutant-selecting antiserum in nature is likely to be a rare event

Topics: QR355
Publisher: Cambridge University Press
Year: 1997
OAI identifier: oai:wrap.warwick.ac.uk:3020

Suggested articles

Preview

Citations

  1. (1994). A novel escape variant (ala 144) of hepatitis B virus in an identical doi
  2. (1978). adaptive and adsorbtive variants of the in¯uenza A hemagglutinin. doi
  3. (1995). All rabbits immunized with type A in¯uenza virions have a serum antibody haemagglutination-inhibition antibody response biased to a single epitope in antigenic site B. doi
  4. (1990). Emergence of viruses resistant to neutralization by V3-speci®c antibodies in experimental human immunode®ciency virus type 1 IIIB infection of chimpanzees.
  5. (1992). Evolution and ecology of in¯uenza A viruses. Microbiol Rev
  6. (1981). Frequency of naturally occurring antibody to in¯uenza virus antigenic variants selected in vitro with monoclonal antibody. doi
  7. (1988). Generation of a neutralization-resistant variant of HIV-1 is due to selection for a point mutation in the envelope gene. Cell doi
  8. (1980). Haemagglutinin-inhibition antibodies in human sera to an antigenic mutant of in¯uenza A}Texas}1}77 (H3N2) virus obtained in vitro. doi
  9. (1993). Immune escape by human immunode®ciency virus type 1 from neutralizing antibodies: evidence for multiple pathways.
  10. (1995). Immunodominance with progenitor B cell diversity in the neutralizing antibody repertoire to in¯uenza infection. doi
  11. (1982). Inactivated in¯uenza virus vaccines.
  12. (1965). Isolation of variant strains from footand-mouth disease virus propagated in cell cultures containing antiviral serum. doi
  13. (1965). Isolation of variants during passage of a strain of foot-and-mouth disease virus in partly immunized cattle. doi
  14. (1996). Longitudinal study of an epitope-biased haemagglutination-inhibition antibody response in rabbits immunized with type A in¯uenza virus. Vaccine doi
  15. (1992). Modi®cation of foot-and-mouth disease virus 01 Caseros after serial passages in the presence of antiviral polyclonal sera. doi
  16. (1994). Modulation of immunodominant sites in in¯uenza hemagglutinin compromise antigenic variation and select receptorbinding variant viruses. doi
  17. (1994). Neutralization escape mutants of type A in¯uenza virus are readily selected by antiserum from mice immunized with whole virus: a possible mechanism for antigenic drift. doi
  18. (1993). Neutralizingantibodyresponseduringhumanimmunode®ciency virus type 1 infection: type and group speci®city and viral escape.
  19. (1950). Persistent antigenic variation of in¯uenza A viruses after incomplete neutralization in ovo with heterologous immune serum. doi
  20. (1990). Rapid development of isolate-speci®c neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS doi
  21. (1993). Resistance of a human serum-selected human immunode®ciency virus type 1 to neutralization by CD4 binding site monoclonal antibodies is conferred by a single amino acid change in gp120.
  22. (1993). Role of conserved glycosylation sites in maturation and transport of in¯uenza A virus hemagglutinin.
  23. (1968). Selection of antigenic mutants of in¯uenza viruses. Isolation and peptide mapping of their hemagglutinating proteins. Virol doi
  24. (1990). Speci®c structural alteration of the in¯uenza haemagglutinin by amantadine.
  25. (1981). Strain speci®city of serum antibody to the haemagglutinin of in¯uenza A (H3N2) viruses in children following immunization or natural infection. doi
  26. (1990). Structural basis of immune recognition of in¯uenza virus hemagglutinin. Ann Rev Immunol doi
  27. (1981). Structural identifcication of the antibody-binding sites of Hong Kong in¯uenza haemagglutinin and their involvement in antigenic variation. doi
  28. (1991). TemoltzinPalaciosF.Structuralassignmentsofnovelandimmunodominant antigenic sites in the neutralizing antibody response of CBA}Ca mice to in¯uenza virus.
  29. (1951). The 1951 in¯uenza virus.
  30. (1990). V region gene usage and somatic mutation in the primary and secondary responses to in¯uenza virus hemagglutinin.
  31. (1990). Vaccine escape mutants of hepatitis B virus. Lancet doi
  32. (1986). WangM-L,SkehelJJ,WileyDC.Comparativeanalyses of the speci®cities of anti-in¯uenza hemagglutinin antibodies in human sera.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.