+Timos Papagatsias
Applying computational approaches to immunogen selection and modification has set new standards in vaccine design. Consider codon optimization, a method which allowed scientists to circumvent codon usage bias in order to achieve high levels of difficult-to-express proteins outside their native hosts. Codon optimization has helped immensely in the development of HIV prototype vaccines where viral genes (gag, env, pol etc.) were expressed in the absence of the Rev-RRE system.
Achieving efficient expression of a vaccine agent in the target tissue/cell, however, does not always guarantee the desired immunogenic effect; and this is where companies like EpiVax can be very useful. Using the tools and technologies available by the company, one can identify putative T cell epitopes (EpiMatrix), MHC Class II epitope clusters (ClustiMer), human(or other species)-like peptides (BlastiMer), de-immunize a protein sequence (thereby creating alternative candidates with altered immunogenic profiles) (OptiMatrix-in combination with their DeFT service) and finally identify conserved epitopes (Conservatrix) in multiple sequences of highly mutating pathogens, such as HIV. The company has also recently introduced VaccineCAD, which is a vaccine-design algorithm that assists in alignment of selected immunogenic epitopes in a vaccine construct, avoiding (or at least reducing) the formation of "nonsense" epitopes, usually appearing at junctions between consecutive epitopes. If you want to check out the web versions of all of EpiVax's tools, head over to the iVAX website.
EpiVax looks a promising company with services that are already finding their way in multiple stages of vaccine design. In addition, we are convinced that its DeFT service can have a significant impact in the field of Gene Therapy, where de-immunization of transgenes is of paramount importance. The company has received several awards from the NIH and it is now making good strides in establishing itself as an one-stop-shop for immunoinformatics. For some more information, here is an article by EpiVax's Founder, CEO and CSO, Dr Annie De Groot.
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Now the company is making waves once again by licensing out its proprietary GLA (Glucopyranosyl Lipid Adjuvant) to MedImmune, for it to be used as an immunomodulating agent in vaccines for select infectious diseases. GLA is a TLR-4 agonist and is considered to be the next generation of MPL (Monophosphoryl Lipid A), an adjuvant originally developed by Corixa and currently being used in vaccines produced by GSK, following the latter's acquisition of Corixa. GLA was originally licensed to Immune Design by the Infectious Disease Research Insitute, IDRI, of Seattle. Immune Design's approach to vaccine design and development is pretty straightforward: targeting of dendritic cells (DC) with their proprietary vector (DC-NILV, Dendritic Cell targeting Non-Integrating Lentivirus Vector) coupled with GLA. Not surprisingly, and given their “talent” for attracting investment, Immune Design had already been identified as an emerging drug developer by FierceBiotech in 2008. The company has some big names on its Scientific Advisory board. Lary Corey is heavily involved in HIV vaccine clinical trials, Rafi Ahmed is involved in HIV vaccine research as well, David Baltimore developed the prototype lentivirus vector that Immune Design are now using (and of course has received the Nobel prize for the discovery of reverse transcriptase!), Philip Greenberg who works on modulating T-cell responses to viruses, Inder Verma, who develops gene therapy vectors and Ralph Steinman who is credited with the discovery of dendritic cells. Throw in the mix someone like Richard Klausner who was an Executive Director for Global Health at the Bill and Melinda Gates foundation and Director of the National Cancer Institute and you end up with a pretty strong team. David Baltimore and Richard Klausner are also on the board of Directors. Immune Design also has a strong executive team; you can find more info here. Given the structure of the Scientific and Exec boards, Immune Design venturing into the world of HIV vaccines pretty soon looks a real possibility. Although the company appears a promising and investable package, it lacks in variety of antigen delivery systems and adjuvants. Looking at their technology, as shown on their website page, the company seems to have been built around a single vector-adjuvant system, not a particularly "safe" approach-a profitable one so far though, as the GLA licensing deal with MedImmune will give Immune Design $212 million. The ability, however, to directly and specifically target DC is a major advantage and should yield exciting results in the years to come. It can be expected that they will seek to partner with companies that are quite geared towards antigen modification for enhancement of immune responses, such as SEEK (formerly known as PepTcell) a company with universal flu and HIV vaccines in Phase II clinical trials.
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