1887

Abstract

Through extensive isolation of neutralizing mAbs against H3N2 influenza viruses representing the repertoire in a human donor, we examined the relationships between antigenic drift of influenza virus and protective antibodies generated in an infected individual. The majority of mAbs isolated from a donor born in 1960 were divided into three major groups with distinct strain specificity: 1968–1973, 1977–1993 and 1997–2003. In the present study, we developed a new method that allowed us to comprehensively determine the location of epitopes recognized by many mAbs. Original haemagglutinins (HAs) of several strains and chimaeric variants, in which one of the seven sites (A, B1, B2, C1, C2, D or E) was replaced by some other strain-derived sequence, were artificially expressed on the cell surface. The binding activity of mAbs to the HAs was examined by flow cytometry. By using this method, we determined the location of epitopes recognized by 98 different mAbs. Clones that neutralize the 1968–1973 strains bind to site B2/D, A or A/B1. While sites C, E and B were recognized by clones that neutralized the 1977–1993 strains, the majority of these clones bind to site C. Clones that neutralize the 1997–2003 strains bind to site B, A/B1, A/B2 or E/C2.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.026419-0
2011-02-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/2/326.html?itemId=/content/journal/jgv/10.1099/vir.0.026419-0&mimeType=html&fmt=ahah

References

  1. Bebbington, C. R., Renner, G., Thomson, S., King, D., Abrams, D. & Yarranton, G. T.(1992). High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker. Biotechnology (N Y) 10, 169–175.[CrossRef] [Google Scholar]
  2. Ekiert, D. C., Bhabha, G., Elsliger, M. A., Friesen, R. H. E., Jongeneelen, M., Throsby, M., Goudsmit, J. & Wilson, I. A.(2009). Antibody recognition of a highly conserved influenza virus epitope. Science 324, 246–251.[CrossRef] [Google Scholar]
  3. Gerhard, W., Yewdell, J., Frankel, M. E. & Webster, R.(1981). Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature 290, 713–717.[CrossRef] [Google Scholar]
  4. Gerhard, W., Mozdzanowska, K., Furchner, M., Washko, G. & Maiese, K.(1997). Role of the B-cell response in recovery of mice from primary influenza virus infection. Immunol Rev 159, 95–103.[CrossRef] [Google Scholar]
  5. Hay, A. J., Gregory, V., Douglas, A. R. & Lin, Y. P.(2001). The evolution of human influenza viruses. Philos Trans R Soc Lond B Biol Sci 356, 1861–1870.[CrossRef] [Google Scholar]
  6. Ito, W. & Kurosawa, Y.(1993). Development of an artificial antibody system with multiple valency using an Fv fragment fused to a fragment of protein A. J Biol Chem 268, 20668–20675. [Google Scholar]
  7. Kashyap, A. K., Steel, J., Oner, A. F., Dillon, M. A., Swale, R. E., Wall, K. M., Perry, K. J., Faynboym, A., Ilhan, M. & other authors(2008). Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies. Proc Natl Acad Sci U S A 105, 5986–5991.[CrossRef] [Google Scholar]
  8. Koelle, K., Cobey, S., Grenfell, B. & Pascual, M.(2006). Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans. Science 314, 1898–1903.[CrossRef] [Google Scholar]
  9. Nakajima, K., Nobusawa, E., Nagy, A. & Nakajima, S.(2005). Accumulation of amino acid substitutions promotes irreversible structural changes in the hemagglutinin of human influenza AH3 virus during evolution. J Virol 79, 6472–6477.[CrossRef] [Google Scholar]
  10. Okada, J., Ohshima, N., Kubota-Koketsu, R., Ota, S., Takase, W., Azuma, M., Iba, Y., Nakagawa, N., Yoshikawa, T. & other authors(2010). Monoclonal antibodies in man that neutralized H3N2 influenza viruses were classified into three groups with distinct strain specificity: 1968–1973, 1977–1993 and 1997–2003. Virology 397, 322–330.[CrossRef] [Google Scholar]
  11. Okuno, Y., Tanaka, K., Baba, K., Maeda, A., Kunita, N. & Ueda, S.(1990). Rapid focus reduction neutralization test of influenza A and B viruses in microtiter system. J Clin Microbiol 28, 1308–1313. [Google Scholar]
  12. Smith, D. J., Lapedes, A. S., de Jong, J. C., Bestebroer, T. M., Rimmelzwaan, G. F., Osterhaus, A. D. M. E. & Fouchier, R. A. M.(2004). Mapping the antigenic and genetic evolution of influenza virus. Science 305, 371–376.[CrossRef] [Google Scholar]
  13. Sui, J., Hwang, W. C., Perez, S., Wei, G., Aird, D., Chen, L. M., Santelli, E., Stec, B., Cadwell, G. & other authors(2009). Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 16, 265–273.[CrossRef] [Google Scholar]
  14. Throsby, M., van den Brink, E., Jongeneelen, M., Poon, L. L. M., Alard, P., Cornelissen, L., Bakker, A., Cox, F., van Deventer, E. & other authors(2008). Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. Plos One 3, e3942.[CrossRef] [Google Scholar]
  15. Ueda, M., Maeda, A., Nakagawa, N., Kase, T., Kubota, R., Takakura, H., Ohshima, A. & Okuno, Y.(1998). Application of subtype-specific monoclonal antibodies for rapid detection and identification of influenza A and B viruses. J Clin Microbiol 36, 340–344. [Google Scholar]
  16. Underwood, P. A.(1982). Mapping of antigenic changes in the haemagglutinin of Hong Kong influenza (H3N2) strains using a large panel of monoclonal antibodies. J Gen Virol 62, 153–169.[CrossRef] [Google Scholar]
  17. Wang, M. L., Skehel, J. J. & Wiley, D. C.(1986). Comparative analyses of the specificities of anti-influenza hemagglutinin antibodies in human sera. J Virol 57, 124–128. [Google Scholar]
  18. Wiley, D. C., Wilson, I. A. & Skehel, J. J.(1981). Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289, 373–378.[CrossRef] [Google Scholar]
  19. Winter, G., Griffiths, A. D., Hawkins, R. E. & Hoogenboom, H. R.(1994). Making antibodies by phage display technology. Annu Rev Immunol 12, 433–455.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.026419-0
Loading
/content/journal/jgv/10.1099/vir.0.026419-0
Loading

Data & Media loading...

Supplements

vol. , part 2, pp. 326 - 335

Construction of plasmid DNAs for cell-surface expression of HA and chimaeric HAs

Nucleotide sequences of the primers used in PCR for construction of chimaeric HA genes [Single PDF file](130 KB)



PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error