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Vectored vaccines can be generated rapidly using recombinant techniques, and manufactured and purified quickly, allowing vaccine production in a short time. Development of non-replicating vectors further amplifies the safety margin and enhances the compliance rate.
Vaxin uses the PER.C6© cell line, licensed from the Dutch biotechnology company Crucell©, as the manufacturing substrate for production of RCA-free adenovirus-vectored vaccines. The advantage of using this highly-characterized cell line is that it permits the production of high-titer recombinant adenovirus vectors that do not replicate in animals or humans. This is a very important feature in terms of product safety. Moreover, Vaxin Scientists have developed the novel AdHigh system for rapid generation of RCA-free adenovirus vectors in PER.C6 cells within one month. The disadvantages associated with adenovirus vectors during gene therapy trials (e.g., transient transgene expression from the vector; hexon-mediated adjuvant effect) appear as remarkable advantages when the vector is used as a vaccine carrier. Effective immunization by adenovirus-vectored nasal vaccines in the presence of pre-existing immunity to adenovirus has been demonstrated in animal models and early phase human studies.
In a phase I human clinical trial, a replication-defective adenovirus vector encoding an influenza hemagglutinin (HA) gene was administered to healthy volunteers. The adenovirus-vectored vaccine was safe when administered intranasally or topically. The immune response was more robust following intranasal delivery and provides the foundation for continued clinical development.
In addition to adenovirus-vectored vaccines, Vaxin Scientists have demonstrated that animals could be effectively immunized against live pathogens (e.g., Clostridium tetani cells and Bacillus anthracis spores) by topical application of non-replicating Escherichia coli (laboratory strains) vectors overproducing pathogen-derived antigens. This novel vaccination modality is amenable to large-scale, rapid, low-cost production, distribution, and administration for vaccination in general, and specifically for mass immunizations.
Vaxin scientists and their associates have also shown that intranasal co-administration of adenovirus vectors encoding α-amyloid β-protein (Aβ) and granulocyte macrophage colony stimulating factor (GMCSF) could reduce amyloid load in the brain of transgenic Alzheimer mice without any appreciable side effects. The impact of this development would be great if this approach should prove effective in human Alzheimer patients.
In addition to the development of human vaccines, Vaxin Scientists and their associates have effectively immunized chickens against avian influenza by in ovo inoculation of non-replicating adenovirus-vectored avian influenza vaccines. This mode of vaccination is expected to emerge as a cost-effective approach for immunizing poultry en masse because adenovirus-vectored vaccines can be produced rapidly in response to emergence of new avian influenza virus strains. Moreover, the non-replicating vector is not associated with any biohazards and can be administered into a large number of embryonated eggs by a robotic injector in a time- and labor-saving manner.
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