Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors

Xiaocong Yu, Tshidi Tsibane, Patricia A. McGraw, Frances S. House, Christopher J. Keefer, Mark D. Hicar, Terrence M. Tumpey, Claudia Pappas, Lucy A. Perrone, Osvaldo Martinez, James Stevens, Ian A. Wilson, Patricia Aguilar, Eric L. Altschuler, Christopher F. Basler, James E. Crowe

Research output: Contribution to journalArticle

259 Citations (Scopus)

Abstract

Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era. Recent work has recovered the gene sequences of this unusual strain, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes. However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure - well into the tenth decade of life.

Original languageEnglish (US)
Pages (from-to)532-536
Number of pages5
JournalNature
Volume455
Issue number7212
DOIs
StatePublished - Sep 25 2008
Externally publishedYes

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Pandemics
Neutralizing Antibodies
Human Influenza
B-Lymphocytes
Viruses
Hemagglutinins
Orthomyxoviridae
Antibodies
H1N1 Subtype Influenza A Virus
Adaptive Immunity
Virus Diseases
Serology
Genes
Antibody Formation
Virulence
Proteins
Swine
Monoclonal Antibodies
Phenotype
Antigens

ASJC Scopus subject areas

  • General

Cite this

Yu, X., Tsibane, T., McGraw, P. A., House, F. S., Keefer, C. J., Hicar, M. D., ... Crowe, J. E. (2008). Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature, 455(7212), 532-536. https://doi.org/10.1038/nature07231

Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. / Yu, Xiaocong; Tsibane, Tshidi; McGraw, Patricia A.; House, Frances S.; Keefer, Christopher J.; Hicar, Mark D.; Tumpey, Terrence M.; Pappas, Claudia; Perrone, Lucy A.; Martinez, Osvaldo; Stevens, James; Wilson, Ian A.; Aguilar, Patricia; Altschuler, Eric L.; Basler, Christopher F.; Crowe, James E.

In: Nature, Vol. 455, No. 7212, 25.09.2008, p. 532-536.

Research output: Contribution to journalArticle

Yu, X, Tsibane, T, McGraw, PA, House, FS, Keefer, CJ, Hicar, MD, Tumpey, TM, Pappas, C, Perrone, LA, Martinez, O, Stevens, J, Wilson, IA, Aguilar, P, Altschuler, EL, Basler, CF & Crowe, JE 2008, 'Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors', Nature, vol. 455, no. 7212, pp. 532-536. https://doi.org/10.1038/nature07231
Yu X, Tsibane T, McGraw PA, House FS, Keefer CJ, Hicar MD et al. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature. 2008 Sep 25;455(7212):532-536. https://doi.org/10.1038/nature07231
Yu, Xiaocong ; Tsibane, Tshidi ; McGraw, Patricia A. ; House, Frances S. ; Keefer, Christopher J. ; Hicar, Mark D. ; Tumpey, Terrence M. ; Pappas, Claudia ; Perrone, Lucy A. ; Martinez, Osvaldo ; Stevens, James ; Wilson, Ian A. ; Aguilar, Patricia ; Altschuler, Eric L. ; Basler, Christopher F. ; Crowe, James E. / Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. In: Nature. 2008 ; Vol. 455, No. 7212. pp. 532-536.
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AU - Wilson, Ian A.

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