Structural interaction between antibodies against human cytomegalovirus and their epitopes and its implication for antibody biological activity

Informations projet

N° de convention de subvention: BIO4980407

Projet clôturé

Date de début 1 Octobre 1998

Date de fin 30 Septembre 2000

Financé au titre de

• Specific research, technological development and demonstration programme in the field of biotechnology, 1994-1998

Coût total

Aucune donnée

Contribution de l’UE

Aucune donnée

Coordonné par

LUND UNIVERSITY
Sweden

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Résultats exploitables

Structural and Functional interaction of ctyomegalovirus glycoprotein B and specific human antibodies.

The primary objectives of this programme is to develop and use structure determination and immunotechnological methods to define major parameters involved in antibody mediated neutralization of an important human pathogen - cytomegalovirus (CMV). This basic knowledge will be used to design antibodies with perfected virus neutralizing properties. We are evolving antibodies specific for a virus protein, glycoprotein B (gB), to make them more potent in their capacity to neutralize the infective properties of the virus. Such information may be used to combat this sometimes clinically difficult and dangerous infection. In order to understand the interactions between these virus-neutralizing antibodies and their viral protein targets we are investigating the relationship between structural interaction and biological activity. We have used antibody gene library technology in combination with phage display to identify variants of previously existing antibodies. Recombination antibody fragments are produced in Pichia pastoris and purified to homogeneity. These proteins are being used to identify how each antibody actually interacts with this viral protein using NMR technology. Such information will be correlated with the specificity characteristics as well as the biological activity that each specific interactions for the biological activity that each specific antibody has against prototype viral strains as well as against naturally occurring, circulating clinical isolates, to define the importance of certain specific interactions for the biological activity. The project brings together laboratories specializing in different specific approaches required to solve this task. Technologies of molecular evolution, protein production and purification, specificity and biological activity studies as well as structural studies are all employed to complete the task successfully.