Infectious Disease (viruses)
RSV. Trellis’ first application of its CellSpot™ technology focused on Respiratory Syncytial Virus (RSV). The antigen of interest was a highly conserved epitope on the virus G protein implicated in sabotage of the host immune response. This epitope proved to be very poorly immunogenic. Over 20 million B cells were screened, from 30 human donors all of whom had recovered from recent RSV infection. A suite of ~10 antibodies with exquisite specificity for the conserved epitope was cloned, with affinities ranging from 1 to 500 pM (i.e., much better than a typical hybridoma or phage display result). In preclinical animal studies, these antibodies showed superior activity as a post-infection therapeutic compared to the currently marketed mAb for RSV (Syngagis™) which is only approved for pre-infection prophylactic use. This project was partnered at the end of 2009 with the leader in the RSV mAb field, MedImmune (a division of Astra Zeneca).
Influenza. Trellis has extended its RSV collaboration with Ralph Tripp at University of Georgia to include other respiratory viruses, notably including influenza. The same discovery strategy used for RSV has yielded very high affinity human antibodies with broad spectrum activity against clinically important strains of influenza. In preliminary animal experiments, the lead candidate has shown superior activity as a post-infection antiviral agent when compared to the best previously described antibody with comparable breadth of activity against clinical strains.
CMV. Infection by cytomegalovirus (CMV) in pregnant women who have not previously been exposed to this virus is the leading non-genetic cause of birth defects (primarily hearing loss). Accordingly, development of a vaccine against CMV has been a high priority for several decades, with the best vaccine to date only providing ~50% protection. This result is particularly frustrating since serum from immune donors has proven to be nearly 100% effective. The key to success in this area appears to be a requirement for very high affinity antibodies, which vaccines have been unable to induce in a consistent manner. Trellis has isolated several high affinity human monoclonal antibodies and is evaluating them in model systems.