Shiloh
Editor, Senior Moderator
Source: http://www.rsc.org/Publishing/Journals/cb/Volume/2009/9/Measles.asp
A structured approach to measles
08 July 2009
European scientists are one step closer to a new measles vaccine, which they say may be suitable for very young infants among the most at risk from the disease.
"Measles is a highly infectious disease, killing 197 000 people in 2007"
Annemieke Madder, from Ghent University, and colleagues in Belgium and Luxembourg have made a molecule that combines a fragment of a measles virus protein with a derivative of cholic acid - a bile acid made naturally in the liver. The acid derivative is attached to the protein fragment in a cyclic fashion, so that it acts as a scaffold to maintain the fragment's helical shape. The structure stabilises the protein fragment in biological fluids. The aim is to prevent the body from breaking it down until it has invoked an immunological response.
Madder says that 'such a construct could find application in modern vaccine technology, which has been evolving towards the inclusion of only the most essential virus parts or derivatives in new formulations for the prevention and treatment of a great number of diseases.' The team has already demonstrated that antibodies known to bind to the measles virus also successfully bind to the construct.
Measles is a highly infectious disease, killing 197 000 people in 2007. Currently a live-attenuated vaccine - a weakened version of the live virus - is used to prevent the disease. But this vaccine is usually given to babies only after around 6-9 months as at an earlier age it can be destroyed by vaccine-neutralising maternal antibodies. Maternal antibodies also destroy the disease itself, but these antibodies, particularly in babies in developing countries, can wane at an early age, leaving infants vulnerable to the disease. Vaccines based on virus fragments can overcome these problems as they avoid detection by maternal antibodies but are still able to stimulate antibody formation. Madder says that such vaccines could possibly be given at a much younger age.
"This work showcases an elegant solution to the problem of conformational control in peptides"
- Anthony Davis
'This work showcases an elegant solution to the problem of conformational control in peptides,' says Anthony Davis, an expert in bile acid scaffolds from the University of Bristol, UK. 'Bile acids have been used as functionalised scaffolds in a number of other areas, but this extension into vaccine design is novel and seems to be very promising,' he says.
To move this project forward Madder's team will next be looking into applying well-known reactions - such as Click chemistry - to make the cyclic peptide conjugates.
Jennifer Newton
Link to journal article
Towards the conformational mimicry of the measles virus HNE loop: design, synthesis and biological evaluation of a cyclic bile acid?peptide conjugate
Catherine A. Bod?, Tom Bechet, Emmanuel Prodhomme, Katelijne Gheysen, Pieter Gregoir, Jos? C. Martins, Claude P. Muller and Annemieke Madder, Org. Biomol. Chem., 2009
DOI: 10.1039/b907395g
A structured approach to measles
08 July 2009
European scientists are one step closer to a new measles vaccine, which they say may be suitable for very young infants among the most at risk from the disease.
"Measles is a highly infectious disease, killing 197 000 people in 2007"
Annemieke Madder, from Ghent University, and colleagues in Belgium and Luxembourg have made a molecule that combines a fragment of a measles virus protein with a derivative of cholic acid - a bile acid made naturally in the liver. The acid derivative is attached to the protein fragment in a cyclic fashion, so that it acts as a scaffold to maintain the fragment's helical shape. The structure stabilises the protein fragment in biological fluids. The aim is to prevent the body from breaking it down until it has invoked an immunological response.
Madder says that 'such a construct could find application in modern vaccine technology, which has been evolving towards the inclusion of only the most essential virus parts or derivatives in new formulations for the prevention and treatment of a great number of diseases.' The team has already demonstrated that antibodies known to bind to the measles virus also successfully bind to the construct.
Measles is a highly infectious disease, killing 197 000 people in 2007. Currently a live-attenuated vaccine - a weakened version of the live virus - is used to prevent the disease. But this vaccine is usually given to babies only after around 6-9 months as at an earlier age it can be destroyed by vaccine-neutralising maternal antibodies. Maternal antibodies also destroy the disease itself, but these antibodies, particularly in babies in developing countries, can wane at an early age, leaving infants vulnerable to the disease. Vaccines based on virus fragments can overcome these problems as they avoid detection by maternal antibodies but are still able to stimulate antibody formation. Madder says that such vaccines could possibly be given at a much younger age.
"This work showcases an elegant solution to the problem of conformational control in peptides"
- Anthony Davis
'This work showcases an elegant solution to the problem of conformational control in peptides,' says Anthony Davis, an expert in bile acid scaffolds from the University of Bristol, UK. 'Bile acids have been used as functionalised scaffolds in a number of other areas, but this extension into vaccine design is novel and seems to be very promising,' he says.
To move this project forward Madder's team will next be looking into applying well-known reactions - such as Click chemistry - to make the cyclic peptide conjugates.
Jennifer Newton
Link to journal article
Towards the conformational mimicry of the measles virus HNE loop: design, synthesis and biological evaluation of a cyclic bile acid?peptide conjugate
Catherine A. Bod?, Tom Bechet, Emmanuel Prodhomme, Katelijne Gheysen, Pieter Gregoir, Jos? C. Martins, Claude P. Muller and Annemieke Madder, Org. Biomol. Chem., 2009
DOI: 10.1039/b907395g