The London-based company has completed a series-A equity funding round with Novartis Venture Fund, Truffle Capital, HealthCap and The London Technology Fund investing £3.5m in the company's synthetic vaccine technology that has been designed to target genetically diverse mutating viruses. In addition, ITS has been awarded an 'exceptional development grant' for £0.5m by the London Development Agency. The last century has seen three flu pandemics caused by various strains of the influenza virus, the most serious of these, the 'Spanish flu' 1917-1918 pandemic, is estimated to have killed over 40m people. With the ever increasing concerns about avian flu (most notably the H5N1 strain) crossing from birds to humans and causing a pandemic flu outbreak, the need for an effective vaccine that can be stockpiled while avoiding the bottlenecks usually seen in vaccine manufacture is becoming ever more pressing. Indeed, the World Health Organisation (WHO) announced earlier today that it was advancing its plans to create a global stockpile of H5N1 vaccines after reaching supply agreements with GlaxoSmithKline (GSK), Omnivest, Baxter and Sanofi-Pasteur. Conventional vaccines generate antibodies that target the outer surface of viruses and these are one of the first mutations to occur to cause antibody resistance. This means that specific vaccines must be produced each year as new mutations occur. According to Carlton Brown, CEO of ITS, the surface antigens of the influenza, HIV and Hepatitis C viruses can vary as much as 75 per cent,while internal antigens mutate much less readily and show a lesser degree of variation. This led ITS to target its synthetic fluoropeptide vaccine molecules at internal virus antigens that are processed by the HLA (human leukocyte antigen) system. The company is still researching the exact mechanism of action of these synthetic vaccines but have observed that they avoid the need for the typical prime-boost strategies needed for non-synthetic vaccines. "We know that with this class of vaccine there is dendritic cell uptake by endocytosis and cross presentation so that you get class I and class II antigen presentation which leads to both CD4 and CD8 responses with a TH1 cytokine profile," said Brown. "The key thing is that because the vaccine molecules are synthetic they continuously reengage the dendritic cells, unlike viral vectors or DNA where tolerance effects can hinder their efficacy." ITS said it uses a proprietary bioinformatics antigen identification platform to identify the antigens most frequently targeted by infected individuals, and has designed its peptides to have high antigenicity profile and target those regions most frequently related to disease control. "If you take blood cells from people with HIV or Hepatitis C and effectively reverse engineer the immune responses that they are making, what you find is that our peptides are targeting those most frequently targeted regions of the virus," said Brown. The fluoropeptide molecules are synthesised using industry standard solid-supported peptide synthesis techniques, which allow the peptides to reflect the genetic diversity of the viruses as well as human diversity. "One of the ways that the synthetic peptide vaccine field has failed over the years is in not accounting for human genetic diversity. A vaccine must reflect both viral and genetic diversity and those are some of the key things we focus on in vaccine design," said Brown. In order to do this, the molecules have to code for a certain amount of genetic information and Brown said in an interview that the molecules were larger than epitopes (chains of between 8 and 11 amino acids) but not as long as full length peptides. "The key limitation is the optimal length of the peptide that can be synthesised effectively, if the peptides are too long you can have yield issues and if they are two short they don't cover sufficient human or viral genetic diversity, we have found what we believe to be an optimal length to cover both these issues," said Brown. Brown believes that the company's lead influenza vaccine is about two years away from the clinic with ITS being in the lead optimisation stage and will be developing candidates for HIV and Hepatitis C in the near future.