The $597,000 grant will go towards a Dengue fever vaccine which makes use of VaxInnate's innovative TLR technology, potentially creating the first and only vaccine for this type of infection. The company's development programme hopes to be able to produce a vaccine capable of protecting against all four different serotypes of the Dengue virus. "The greatest difficulty in developing a tetravalent vaccine has been in formulation," Jeff Powell, vice president of research, and William McDonald, group leader of biochemistry at the company explained to US-PharmaTechnologist.com "A balanced immune response against all four serotypes is critical and this has been the greatest challenge to others who are developing whole live-virus vaccines. Delivering four recombinant fusion proteins as a tetravalent cocktail offers control and flexibility in developing an optimal antigen ratio." VaxInnate, in collaboration with the University of Texas Medical Branch (UTMB), hopes to be able to achieve this tetravalent protection by using the company's TLR technology to develop a vaccine where other production methods have failed. The NIH grant to support the development of a Dengue fever vaccine comes on the back of positive proof of principle studies in West Nile virus, which showed that the TLR technology could have applications in a number of Flavivirus diseases, including Dengue fever. "This funding allows us to utilize this technology to formulate the correct ratio of the different serotypes of Dengue virus proteins to develop a tetravalent vaccine," Jeff Powell, vice president of research at the company explained. The proceeds of the award, which comes under the Small Business Innovation Research grant scheme at the NIH, will be used to support pre-clinical research on a Dengue virus vaccine based on the TLR technology, with animal tests expected to begin next year. The TLR - toll-like receptor - platform is formed around the ability of toll-like receptors to recognize certain molecular patterns and trigger an innate immune response. While the innate immune response is very fast, it is not pathogen-specific, and may have limited capability in staving off some infections. As such, VaxInnate have harnessed the power of the highly specific adaptive immune system in combination with the innate immune response. By linking the molecular patterns recognized in the innate response to an antigen (the target of the adaptive immune response), strong antibody and immune responses are generated. The vaccines that the company is developing combine proteins of vaccine antigen and bacterial flagellin, one of the molecular patterns recognized by TLRs. According to the company, physically linking flagellin to antigens results in a more potent immune response than simply administering a mixture of the two separate components. The company's most advanced product making use of the TLR technology is a universal flu vaccine, which consists of the TLR5 ligand flagellin fused to a conserved region of the influenza virus, M2e. Clinical evaluation of the vaccine is due to begin in the next few weeks. Although the influenza virus is the key target in the company's vaccine development plans, the TLR technique has also been shown to stimulate robust protective immune responses in animal models to West Nile virus, Japanese encephalitis virus, malaria and listeria infection. The manufacturing process for VaxInnate's vaccines also offers advantages over traditional egg-based production, according to the company. The fusion products are relatively simple to make using recombinant DNA techniques, and can be efficiently and economically manufactured in bacteria much more rapidly than vaccines using cumbersome egg-based manufacturing methods. "A major advantage of the E.Coli production platform is the ease of transferring the production to a number of sites around the world, including areas such as South America and Asia where Dengue fever and other infectious diseases are endemic," US-PharmaTechnologist.com was told. With no vaccine to treat Dengue virus currently available, and around 2.5 billion people living in areas at risk for pandemic transmission, VaxInnate's product could be a significant weapon in the fight to protect public health in these high risk regions.