on October 6, 2014
BELLINZONA (Switzerland) – A publication in the renowned scientific journal Nature describes a rapid pathway to generate antibodies that broadly neutralize influenza viruses. The study is the result of a collaboration between the Institute for Research in Biomedicine (IRB) which is affiliated to the Università della Svizzera italiana (USI), Humabs BioMed, both in Bellinzona, Switzerland and scientists at MedImmune, the global biologics research and development arm of AstraZeneca, and at the San Raffaele University and Research Hospital in Milano, Italy. The study was supported by the European Research Council, the Swiss National Science Foundation, the National Institute of Health, the Human Frontiers Science Program and the Fondazione Cariplo.
Background
Antibodies are the primary defense mechanism against infections. The antibody genes are assembled from DNA segments present in our genome and are then improved through an iterative process of mutation and selection that takes place in the course of the immune response. High affinity antibodies typically contain up to 20-40 mutations, which are thought to be required for binding and killing of the pathogen.
The discovery
In a paper published in the last issue of Nature, a team of scientists led by Antonio Lanzavecchia (USI) at the institute for Research in Biomedicine and Davide Corti at Humabs BioMed, in collaboration with colleagues at MedImmune and Elisa Vicenzi, Head of Unit – Viral pathogens & biosafety – San Raffaele University and Research Hospital, has been able to reconstruct the genealogy tree of a particular type of antibodies that can neutralize multiple species of influenza viruses (so-called broadly neutralizing antibodies). These antibodies bind to a conserved site on the influenza hemagglutinin that represents the Achilles’ heel of the virus. There is a great interest to develop a universal influenza vaccine that can induce these types of antibodies. In addition, the antibodies themselves are potential therapeutic agents for the treatment and/or prevention of influenza.
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| Figure showing a structural model of antibody with its characteristic Y shape, in which the single key mutation is highlighted in red, while the further mutations, introduced during its maturation are highlighted in yellow. |
The new and unexpected finding is that a single initial somatic mutation is sufficient to achieve maximal binding and neutralization of the virus, while the numerous mutations that occur at later time points are essentially redundant. This means that these antibodies can be generated rapidly. “We found that there are plenty of precursors in our body that can rapidly generate, with just a single mutation, potent neutralizing antibodies. This suggests that it should be possible to elicit, with an appropriate vaccine, high levels of antibodies that protect against all influenza viruses” comments Antonio Lanzavecchia, senior author of the study.
The new study also shows that the making of these antibodies requires a particular gene segment (called VH1-69), which occurs in the population in two different forms, of which only one can give rise to a broadly neutralizing antibody. “We found that rare individuals lacking these gene segments cannot make these antibodies. However, with time, these individuals can develop antibodies with similar properties using other gene segments”, comments Davide Corti.
About the Institute for Research in Biomedicine (IRB) and the Università della Svizzera italiana (USI). The Institute for Research in Biomedicine (IRB), founded in 2000 in Bellinzona, has been affiliated to the Università della Svizzera italiana (USI) in 2010. Financed by private and public institutions, and by competitive grants, the IRB currently hosts nine research groups and 90 researchers. Research focuses on the human host defense against infections, tumors and degenerative diseases. With more than 370 publications in leading scientific journals, the IRB has gained an international reputation as a center of excellence in immunology. www.irb.usi.ch
About Humabs BioMed. Humabs is a privately owned Swiss Biotech company incorporated as a spin-off of the Institute for Research in Biomedicine (IRB). The company discovers and develops next-generation fully human monoclonal antibodies. The discovery technologies have been developed at the IRB by Professor Dr. Antonio Lanzavecchia and have been out licensed to Humabs in 2004. Humabs is focusing on the creation of unique antibodies to treat infectious and inflammatory diseases for clinical development through pharmaceutical partners. The company has already partnered with two major pharmaceutical companies for taking two of its programs, anti HCMV and anti Flu A & Flu B antibodies, to clinical development. www.humabs.com
Article reference: Pappas L. , Foglierini M. , Piccoli L. , Kallewaard N. , Turrini F. , Silacci C. , Fernandez-Rodriguez B. , Agatic G. , Giacchetto-Sasselli I. , Pellicciotta G. , Sallusto F. , Zhu Q. , Vicenzi E. , Corti D. & Lanzavecchia A. “Rapid development of broadly influenza neutralizing antibodies through redundant mutation”. Advance Online Publication (AOP) on: http://www.nature.com/nature
