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

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Clin Infect Dis. 2011 Apr;52(8):1003-9.
Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza a antibodies.

Sui J, Sheehan J, Hwang WC, Bankston LA, Burchett SK, Huang CY, Liddington RC, Beigel JH, Marasco WA.

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute.
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.

PMID: 21460314 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/21460314

 

[tetano]

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

Prospecting the Influenza Hemagglutinin to Develop Universal Vaccines




1. Ruben O. Donis and
2. Nancy J. Cox

1.
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

1. Correspondence: Nancy J. Cox, PhD, Influenza Branch G-16 Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333 (njc1{at}cdc.gov).

(See the article by Sui et al, on pages 1003?1009 .)

Influenza pandemics are among the most serious infectious threats to public health. The 1918?1919 influenza pandemic caused up to 500,000 deaths during a single influenza season in the United States, representing the most fatalities within such a short period in US public health history. The 2009 H1N1 influenza pandemic caused much less mortality but nevertheless exposed important limitations of global pandemic preparedness. [ 1, 2, 3]. First, the 2009 H1N1 virus was not detected by animal health surveillance systems for >10 years, exposing the inadequacy of current surveillance for viruses in animals that have pandemic potential for humans [ 4]. Second, the emergence of a pandemic virus with the same HA and NA subtypes as viruses that had been circulating in humans for decades (seasonal H1N1 virus) underscored the need to better understand immunity to emerging influenza viruses in the human population [ 4]. Finally, the 2009 H1N1 pandemic exposed our current inability to develop, manufacture, deliver, and administer billions of doses of vaccine directed against a newly emerging virus in the 4 months or less that would have been required to mitigate the impact of the spread of the 2009 H1N1 virus. [ 5]. Thus, several strategic changes in pandemic vaccine preparedness plans have been recommended [ 6]. The proposed changes are costly and often not affordable for low- and middle-income countries. Thus, sustainable long-term solutions will require the development of novel immunization strategies. The concept of a universal influenza vaccine that would elicit protection against a broad ?


http://cid.oxfordjournals.org/content/52/8/1010.extract