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Neurome Technologies Discovery Screening Vaccine Gallery

The mucosal immune system is responsible for surveillance of infectious agents and triggering antibody responses to these agents. In the gut, this mechanism is dependent on an active sampling of intestinal contents by specialized cells, called M cells, which transport antigens and microparticles to the underlying immune tissue. This transport, called transcytosis, relies on specific receptors able to selectively bind antigens and microorganisms posing the greatest threat. Using TOGA®, Neurome has identified these epithelial cell transcytosis receptors. Such receptors are ideal targets for vaccine delivery systems, and Neurome is developing a new technology that takes advantage of these specialized receptors for targeted, receptor-mediated delivery of specialized synthetic vaccines to mucosal sites such as the nasal epithelium and small intestine.

Technology
The current understanding of mucosal immune surveillance points to a critical role for M cells in the active transcytosis of antigens and particles from the intestinal lumen to the underlying lymphoid tissue.

Until now, the difficulties in isolating M cells have limited the scientific understanding of their function, and the array of receptors responsible for transcytosis. To identify the critical genes involved in M cell function, we used Neurome’s highly sensitive and quantitative technology, TOGA®, to identify those genes specifically expressed in induced M cells. TOGA® permits the accurate identification of genes with regulated expression among extremely small cell or tissue samples, and when applied to samples of human intestinal epithelium cell lines and microdissected animal tissues, yielded several candidate target receptors.

Fluorescence images of intestinal Peyer's Patch, stained with a fluorescent lectin specific for M cells (red) and with fluorescent in situ hybridization probe specific for an M cell specific gene transcript (green). The overlaid image shows co-localization of the lectin binding and gene expression in the same cells.

These receptor genes were cloned, and their sequences were used to confirm expression in specific tissues and cells (such as M cells) of the mucosal immune system of mice, monkeys, and humans. The genes were also expressed in cell lines, which were then used for experimental selection of synthetic short peptide ligands specific to each candidate receptor.

Development Plan
Neurome is developing an entirely new vaccine delivery technology, using a set of candidate M cell and FAE receptor genes as targets. We are currently developing several candidate formulations for testing in preclinical experiments using mouse models. We are focusing on influenza, since significant market need exists for targeted mucosal vaccines against emerging strains of influenza. We anticipate that initial preclinical studies will be underway by the end of 2005, and will yield key information on the potency of the recombinant vaccine formulations.

Animal Health Applications
Neurome’s vaccine technology may also be applied to homologous receptors in additional animal species, specifically those in important veterinary medicine markets, such as farm animals (chickens, pigs, cows, sheep), horses, and pets such as cats and dogs. The direct benefit to veterinary medicine includes ease of use, and a reduction in the dependency on low-dose antibiotic use.

Market Opportunity
The worldwide market for vaccines is estimated to grow to between $10 and $20 billion in the next five years. Currently available vaccines are targeted to only a small proportion of known infectious agents. Moreover, the technology presently used in vaccine development has not advanced in over sixty years. Present barriers to development of new vaccines include challenges in the cultivation of the infectious agents themselves for extraction of antigens, limited knowledge toward identification of the most immunogenic (and protective) components of the infectious agents, and development of optimal formulations of antigen and adjuvant for effective immunization. Neurome’s vaccine technology addresses these challenges, and provides an opportunity for rapid development of a new class of mucosal vaccines, targeted against a wide variety of infectious agents.

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