Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza a antibodies

Jianhua Sui, Jared Sheehan, William C. Hwang, Laurie A. Bankston, Sandra K. Burchett, Chiung Yu Huang, Robert C. Liddington, John H. Beigel, Wayne A. Marasco

Research output: Contribution to journalArticle

Abstract

(See the editorial commentary by Donis and Cox, on pages 1010-1012.)Background.Lack of life-long immunity against influenza viruses represents a major global health care problem with profound medical and economic consequences. A greater understanding of the broad-spectrum "heterosubtypic" neutralizing human antibody (BnAb) response to influenza should bring us closer toward a universal influenza vaccine.Methods.Serum samples obtained from 77 volunteers in an H5N1 vaccine study were analyzed for cross-reactive antibodies (Abs) against both subtype hemagglutinins (HAs) and a highly conserved pocket on the HA stem of Group 1 viruses. Cross-reactive Abs in commercial intravenous immunoglobulin were affinity purified using H5-coupled beads followed by step-wise monoclonal antibody competition or acid elution. Enzyme-linked immunosorbent assays were used to quantify cross-binding, and neutralization activity was determined with HA-pseudotyped viruses.Results.Prevaccination serum samples have detectable levels of heterosubtypic HA binding activity to both Group 1 and 2 influenza A viruses, including subtypes H5 and H7, respectively, to which study subjects had not been vaccinated. Two different populations of Broadly neutralizing Abs (BnAbs) were purified from intravenous immunoglobulin by H5 beads: ∼0.01% of total immunoglobulin G can bind to HAs from both Group 1 and 2 and neutralize H1N1 and H5N1 viruses; ∼0.001% is F10-like Abs directed against the HA stem pocket on Group 1 viruses.Conclusion.These data - to our knowledge, for the first time - quantitatively show the presence, albeit at low levels, of two populations of heterosubtypic BnAbs against influenza A in human serum. These observations warrant further investigation to determine their origin, host polymorphism(s) that may affect their expression levels and how to boost these BnAb responses by vaccination to reach sustainable protective levels.

Original languageEnglish (US)
Pages (from-to)1003-1009
Number of pages7
JournalClinical Infectious Diseases
Volume52
Issue number8
DOIs
StatePublished - Apr 15 2011
Externally publishedYes

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Hemagglutinins
Human Influenza
Antibodies
Intravenous Immunoglobulins
Viruses
Neutralizing Antibodies
Serum
H5N1 Subtype Influenza A Virus
Medical Economics
H1N1 Subtype Influenza A Virus
Influenza Vaccines
Influenza A virus
Orthomyxoviridae
Population
Antibody Formation
Volunteers
Immunity
Vaccination
Vaccines
Immunoglobulin G

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

Sui, J., Sheehan, J., Hwang, W. C., Bankston, L. A., Burchett, S. K., Huang, C. Y., ... Marasco, W. A. (2011). Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza a antibodies. Clinical Infectious Diseases, 52(8), 1003-1009. https://doi.org/10.1093/cid/cir121

Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza a antibodies. / Sui, Jianhua; Sheehan, Jared; Hwang, William C.; Bankston, Laurie A.; Burchett, Sandra K.; Huang, Chiung Yu; Liddington, Robert C.; Beigel, John H.; Marasco, Wayne A.

In: Clinical Infectious Diseases, Vol. 52, No. 8, 15.04.2011, p. 1003-1009.

Research output: Contribution to journalArticle

Sui, J, Sheehan, J, Hwang, WC, Bankston, LA, Burchett, SK, Huang, CY, Liddington, RC, Beigel, JH & Marasco, WA 2011, 'Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza a antibodies', Clinical Infectious Diseases, vol. 52, no. 8, pp. 1003-1009. https://doi.org/10.1093/cid/cir121
Sui J, Sheehan J, Hwang WC, Bankston LA, Burchett SK, Huang CY et al. Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza a antibodies. Clinical Infectious Diseases. 2011 Apr 15;52(8):1003-1009. https://doi.org/10.1093/cid/cir121
Sui, Jianhua ; Sheehan, Jared ; Hwang, William C. ; Bankston, Laurie A. ; Burchett, Sandra K. ; Huang, Chiung Yu ; Liddington, Robert C. ; Beigel, John H. ; Marasco, Wayne A. / Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza a antibodies. In: Clinical Infectious Diseases. 2011 ; Vol. 52, No. 8. pp. 1003-1009.
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