In a CRADA between NHLBI and MedImmune, a manufacturing process was developed for the VLP vaccine and multiple animal species were tested. Initial studies showed that enrichment of VLPs by manipulating multiplicity of infection (MOI) for the baculoclones could produce capsids containing increased VP1 (20 to 40%), and that such preparations were effective in promoting neutralizing antibody response.
In the first Phase I clinical study, VLPs formulated with aluminum hydroxide elicited low neutralizing antibody titers. A second Phase I study, conducted using VLPs formulated with the Novartis squalene-based MF59c.1 adjuvant yielded excellent neutralizing antibody responses in humans. However, MedImmune ceased development of the vaccine and returned the vaccine rights to the NIH.
Meridian Life Science was then contracted to manufacture the vaccine under cGMP to support further development by NHLBI. Meridian subsequently licensed the vaccine technology, developed a more robust manufacturing process, and successfully manufactured Phase I materials.