Biosafe coronavirus vaccine vector for the prevention of human infections of the enteric and respiratory tract (BIOSAFE-VACCINE-VECTOR)

Informazioni relative al progetto

BIOSAFE-VACCINE-VECT

ID dell’accordo di sovvenzione: QLK2-CT-2001-00874

Progetto chiuso

Data di avvio 1 Dicembre 2001

Data di completamento 27 Febbraio 2005

Finanziato da

• Specific Programme for research, technological development and demonstration on "Quality of life and management of living resources", 1998-2002

Costo totale

€ 2 632 221,00

Contributo UE

€ 1 255 414,00

Coordinato da

CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

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Risultati finali

Application of the vector to the protection against human enteric and respiratory diseases. The vector is being applied to elicit protection against rotavirus infections

The vaccine developed for human rotaviruses still needs to be completed and its biosafety tested in the transgenic animal model developed. Other vaccines for animal health that have been used to improve the quality and biosafety of this type of vector could be ready in 24 months. A candidate vaccine for SARS-CoV, based on a recombinant virus in which an structural gene has been deleted, is being tested in ferrets and monkeys for the moment, in collaboration with Dr. Albert Osterhaus (Rotherdam). If the results are satisfactory it may enter in preclinical trials in 1-2 years.

An experimental animal model to evaluate the human vector, based on a transgenic mice expressing the receptor for the human virus (hAPN) has been obtained by microinjection

Human coronavirus 229E (HCoV-229E) is a serogroup 1 coronavirus and specific to humans. So far no animal model is available to study the pathogenesis of infection by HCoV-229E. We show here that the expression of aminopeptidase N (APN, also termed CD13), the receptor for HCoV-229E, is required but not sufficient to confer susceptibility in vivo. HCoV-229E infection was facilitated by crossing APN transgenic mice into Stat1-null mice and by adaptation of HCoV-229E to grow in primary Stat1-null fibroblasts. Double transgenic mice allow for the first time the study of human coronavirus group 1 infections in an animal model, in particular viral tropism, replication, recombination and spread in an immunocompromised situation. Furthermore, these mice provide an important tool for the evaluation of biosafety and efficacy of coronavirus-based vectors.

A collection of vectors with different attenuation degree has been developed by modifying the sequences that regulate the expression of the different viral genes

A human vector has been developed. As intermediate steps vaccines for animal health have been developed. The vector developed could be applied to the development of vaccines for other diseases. The vaccine developed for human rotaviruses still needs to be completed and its biosafety tested in the transgenic animal model developed. Other vaccines for animal health that have been used to improve the quality and biosafety of this type of vector could be ready in 24 months. A candidate vaccine for SARS-CoV, based on a recombinant virus in which a structural gene has been deleted, is being tested in ferrets and monkeys for the moment, in collaboration with Dr. Albert Osterhaus (Rotterdam). If the results are satisfactory it may enter in preclinical trials in 1-2 years.