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

Deliverables

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.
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 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.

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