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Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors.
Nature. 2008 Sep 25; 455(7212):532-6
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29 Aug 2008
New Finding, Technical Advance
DOI: 10.3410/f.1120317.576487
This is a beautiful study, which demonstrates that you can still learn about the immune response in humans against a pathogen that was circulating almost 100 years ago by analyzing blood samples from people that experienced infections with this pathogen.
Yu et al. describe one that not only can find...Continue reading
Yu et al. describe one that not only can find...Continue reading
This is a beautiful study, which demonstrates that you can still learn about the immune response in humans against a pathogen that was circulating almost 100 years ago by analyzing blood samples from people that experienced infections with this pathogen.
Yu et al. describe one that not only can find antibodies against the influenza virus strain that caused the 1918 flu pandemic in the blood of 91-101 year-old individuals, but also 1918 flu-specific circulating B cells.
They were also able to generate from PBMCs of these individuals hybridoma cell lines that secreted neutralizing antibodies specific for the 1918 and closely antigenically related influenza virus strains. Characterization of these human monoclonal antibodies revealed specific sites in the hemagglutinin surface protein of the 1918 influenza virus recognized by the antibodies, offering a close glimpse at a human immune response generated a century ago.
Yu et al. describe one that not only can find antibodies against the influenza virus strain that caused the 1918 flu pandemic in the blood of 91-101 year-old individuals, but also 1918 flu-specific circulating B cells.
They were also able to generate from PBMCs of these individuals hybridoma cell lines that secreted neutralizing antibodies specific for the 1918 and closely antigenically related influenza virus strains. Characterization of these human monoclonal antibodies revealed specific sites in the hemagglutinin surface protein of the 1918 influenza virus recognized by the antibodies, offering a close glimpse at a human immune response generated a century ago.
Disclosures
None declared
Add Comment
Garcia-Sastre A: F1000Prime Recommendation of [Yu X et al., Nature 2008, 455(7212):532-6]. In F1000Prime, 29 Aug 2008; DOI: 10.3410/f.1120317.576487. F1000Prime.com/1120317#eval576487
30 Sep 2008
David A Groneberg
F1000 Respiratory Disorders
Goethe University Frankfurt,
Frankfurt am Main, Germany.
F1000 Respiratory Disorders
Goethe University Frankfurt,
Frankfurt am Main, Germany.
Confirmation
DOI: 10.3410/f.1120317.580078
This article suggests that circulating B memory cells recognizing the influenza virus or their progeny survive many decades after the initial exposure and retain their ability.
Based on the recently recovered gene sequence of a influenza virus pandemic in 1918, Yu et al. investigated whether subjects...Continue reading
Based on the recently recovered gene sequence of a influenza virus pandemic in 1918, Yu et al. investigated whether subjects...Continue reading
This article suggests that circulating B memory cells recognizing the influenza virus or their progeny survive many decades after the initial exposure and retain their ability.
Based on the recently recovered gene sequence of a influenza virus pandemic in 1918, Yu et al. investigated whether subjects (who in 1918 were 2-12 years old) showed evidence of acquired immunity to the virus. From peripheral blood mononuclear cells (PBMCs) of the subjects, hybridoma cell lines were generated. The monoclonal antibodies proved highly specific to the 1918 virus and genetically similar strains. Furthermore, the antibodies had a high virus-neutralizing potency and protected mice from lethal infections by the 1918 influenza strain. This paper suggests that circulating B memory cells recognizing the influenza virus or their progeny survive many decades after the initial exposure and retain their ability -- knowledge that has already been acquired for plasma cells.
This opens up the enormous possibilities of utilizing the treasures of highly specific antibodies created in past influenza pandemics by individuals who had dealt with the virus immunologically. The authors have used a straight forward model to answer a long-existing question about the natural destiny of B memory cells; however, in regard to the initial and possibly repeated contacts with influenza virus strains, there remains a certain doubt concerning the availability of fully trustable clinical history of the subjects. Therefore, further research should centre on reproducing the result with subjects providing more certain medical histories. Also, other infectious disease should be evaluated.
Based on the recently recovered gene sequence of a influenza virus pandemic in 1918, Yu et al. investigated whether subjects (who in 1918 were 2-12 years old) showed evidence of acquired immunity to the virus. From peripheral blood mononuclear cells (PBMCs) of the subjects, hybridoma cell lines were generated. The monoclonal antibodies proved highly specific to the 1918 virus and genetically similar strains. Furthermore, the antibodies had a high virus-neutralizing potency and protected mice from lethal infections by the 1918 influenza strain. This paper suggests that circulating B memory cells recognizing the influenza virus or their progeny survive many decades after the initial exposure and retain their ability -- knowledge that has already been acquired for plasma cells.
This opens up the enormous possibilities of utilizing the treasures of highly specific antibodies created in past influenza pandemics by individuals who had dealt with the virus immunologically. The authors have used a straight forward model to answer a long-existing question about the natural destiny of B memory cells; however, in regard to the initial and possibly repeated contacts with influenza virus strains, there remains a certain doubt concerning the availability of fully trustable clinical history of the subjects. Therefore, further research should centre on reproducing the result with subjects providing more certain medical histories. Also, other infectious disease should be evaluated.
Acknowledgments
I would like to thank David Quarcoo for their assistance in the preparation of this evaluation.
Disclosures
None declared
Groneberg D: F1000Prime Recommendation of [Yu X et al., Nature 2008, 455(7212):532-6]. In F1000Prime, 30 Sep 2008; DOI: 10.3410/f.1120317.580078. F1000Prime.com/1120317#eval580078
03 Feb 2009
New Finding, Technical Advance
DOI: 10.3410/f.1120317.602439
This study generates human monoclonal antibodies to the 1918 strain of flu and demonstrates the longevity of immunological memory in humans.
The paper describes two important findings. First, in a technically impressive series of experiments, the authors generate human monoclonal antibodies specific...Continue reading
The paper describes two important findings. First, in a technically impressive series of experiments, the authors generate human monoclonal antibodies specific...Continue reading
This study generates human monoclonal antibodies to the 1918 strain of flu and demonstrates the longevity of immunological memory in humans.
The paper describes two important findings. First, in a technically impressive series of experiments, the authors generate human monoclonal antibodies specific for the 1918 strain of H1N1 influenza virus. These antibodies are highly specific, neutralize the virus and can protect mice from lethal infection. Second, the studies reported demonstrate robust humoral immunity (both serological memory and B cell memory) in humans to a pathogen not encountered for ~90 years. These findings indicate that the immunological memory (at least B cell memory) can last a human lifetime.
The paper describes two important findings. First, in a technically impressive series of experiments, the authors generate human monoclonal antibodies specific for the 1918 strain of H1N1 influenza virus. These antibodies are highly specific, neutralize the virus and can protect mice from lethal infection. Second, the studies reported demonstrate robust humoral immunity (both serological memory and B cell memory) in humans to a pathogen not encountered for ~90 years. These findings indicate that the immunological memory (at least B cell memory) can last a human lifetime.
Disclosures
None declared
Wherry E: F1000Prime Recommendation of [Yu X et al., Nature 2008, 455(7212):532-6]. In F1000Prime, 03 Feb 2009; DOI: 10.3410/f.1120317.602439. F1000Prime.com/1120317#eval602439
21 Jul 2011
New Finding, Technical Advance
DOI: 10.3410/f.1120317.13259055
While hybridoma technology still suffers from potentially unstable cell lines, technological strides have increased the efficiency of producing large, representative monoclonal anitbody libraries to the point where elegant studies using human hybridomas are now feasible. This study demonstrates the...Continue reading
While hybridoma technology still suffers from potentially unstable cell lines, technological strides have increased the efficiency of producing large, representative monoclonal anitbody libraries to the point where elegant studies using human hybridomas are now feasible. This study demonstrates the successful isolation of exceedingly rare 1918 Spanish flu pandemic reactive antibodies from three elderly subjects who had been infected over 80 years ago, illustrating the power and sensitivity of this technology.
Characterization of neutralizing antibodies using this technology has permitted these and other investigators to map the structural and functional nuances of molecules contributing to the virulence of influenza, HIV, and other pathogens, which in turn provides targets for the development of new therapeutics and vaccines.
To view the context in which this article was evaluated, see its citation in F1000 Biology Reports: Harnessing the immune system's arsenal: producing human monoclonal antibodies for therapeutics and investigating immune responses by Patrick C. Wilson et al (2011).
Characterization of neutralizing antibodies using this technology has permitted these and other investigators to map the structural and functional nuances of molecules contributing to the virulence of influenza, HIV, and other pathogens, which in turn provides targets for the development of new therapeutics and vaccines.
To view the context in which this article was evaluated, see its citation in F1000 Biology Reports: Harnessing the immune system's arsenal: producing human monoclonal antibodies for therapeutics and investigating immune responses by Patrick C. Wilson et al (2011).
Acknowledgments
Meghan Sullivan, Kaval Kaur and Noel Pauli helped with the writing of this evaluation.
Disclosures
None declared
Wilson P: F1000Prime Recommendation of [Yu X et al., Nature 2008, 455(7212):532-6]. In F1000Prime, 21 Jul 2011; DOI: 10.3410/f.1120317.13259055. F1000Prime.com/1120317#eval13259055
F1000Prime Recommendations, Dissents and Comments for [Yu X et al., Nature 2008, 455(7212):532-6]. In F1000Prime, 25 May 2013; F1000Prime.com/1120317
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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.
DOI: 10.1038/nature07231
PMID: 18716625
