Focused antibody response to influenza linked to antigenic drift

Kuan Ying A Huang, Pramila Rijal, Lisa Schimanski, Timothy J. Powell, Tzou Yien Lin, John W. McCauley, Rodney S. Daniels, Alain R. Townsend

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The selective pressure that drives antigenic changes in influenza viruses is thought to originate from the human immune response. Here, we have characterized the B cell repertoire from a previously vaccinated donor whose serum had reduced neutralizing activity against the recently evolved clade 6B H1N1pdm09 viruses. While the response was markedly polyclonal, 88% of clones failed to recognize clade 6B viruses; however, the ability to neutralize A/USSR/90/1977 influenza, to which the donor would have been exposed in childhood, was retained. In vitro selection of virus variants with representative monoclonal antibodies revealed that a single amino acid replacement at residue K163 in the Sa antigenic site, which is characteristic of the clade 6B viruses, was responsible for resistance to neutralization by multiple monoclonal antibodies and the donor serum. The K163 residue lies in a part of a conserved surface that is common to the hemagglutinins of the 1977 and 2009 H1N1 viruses. Vaccination with the 2009 hemagglutinin induced an antibody response tightly focused on this common surface that is capable of selecting current antigenic drift variants in H1N1pdm09 influenza viruses. Moreover, amino acid replacement at K163 was not highlighted by standard ferret antisera. Human monoclonal antibodies may be a useful adjunct to ferret antisera for detecting antigenic drift in influenza viruses.

Original languageEnglish
Pages (from-to)2631-2645
Number of pages15
JournalJournal of Clinical Investigation
Volume125
Issue number7
DOIs
Publication statusPublished - Jul 1 2015
Externally publishedYes

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Human Influenza
Antibody Formation
Orthomyxoviridae
Viruses
Ferrets
Monoclonal Antibodies
Hemagglutinins
Immune Sera
Amino Acids
H1N1 Subtype Influenza A Virus
USSR
Serum
Vaccination
B-Lymphocytes
Clone Cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Huang, K. Y. A., Rijal, P., Schimanski, L., Powell, T. J., Lin, T. Y., McCauley, J. W., ... Townsend, A. R. (2015). Focused antibody response to influenza linked to antigenic drift. Journal of Clinical Investigation, 125(7), 2631-2645. https://doi.org/10.1172/JCI81104

Focused antibody response to influenza linked to antigenic drift. / Huang, Kuan Ying A; Rijal, Pramila; Schimanski, Lisa; Powell, Timothy J.; Lin, Tzou Yien; McCauley, John W.; Daniels, Rodney S.; Townsend, Alain R.

In: Journal of Clinical Investigation, Vol. 125, No. 7, 01.07.2015, p. 2631-2645.

Research output: Contribution to journalArticle

Huang, KYA, Rijal, P, Schimanski, L, Powell, TJ, Lin, TY, McCauley, JW, Daniels, RS & Townsend, AR 2015, 'Focused antibody response to influenza linked to antigenic drift', Journal of Clinical Investigation, vol. 125, no. 7, pp. 2631-2645. https://doi.org/10.1172/JCI81104
Huang KYA, Rijal P, Schimanski L, Powell TJ, Lin TY, McCauley JW et al. Focused antibody response to influenza linked to antigenic drift. Journal of Clinical Investigation. 2015 Jul 1;125(7):2631-2645. https://doi.org/10.1172/JCI81104
Huang, Kuan Ying A ; Rijal, Pramila ; Schimanski, Lisa ; Powell, Timothy J. ; Lin, Tzou Yien ; McCauley, John W. ; Daniels, Rodney S. ; Townsend, Alain R. / Focused antibody response to influenza linked to antigenic drift. In: Journal of Clinical Investigation. 2015 ; Vol. 125, No. 7. pp. 2631-2645.
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