The production, harvest and adsorptive recovery of an infectious herpes simplex virus vaccine

At present there is not a reliable vaccine against herpes virus. Viral protein vaccines as yet have proved unsuccessful to meet the challenge of raising an appropriate immune response. Cantab Pharmaceuticals has produced a virus vaccine that can undergo one round of replication in the recipient in order to produce a more specific immune reaction. This virus is called Disabled Infectious Single Cycle Herpes Simplex Virus (DISC HSV) which has been derived by deleting the essential gH gene from a type 2 herpes virus. This vaccine has been proven to be effective in animal studies. Existing methods for the purification of viruses rely on laboratory techniques and for vaccine production would be on a far too small a scale. There is therefore a need for new virus purification methods to be developed in order to meet these large scale needs. An integrated process for the manufacture of a purified recombinant DISC HSV is described. The process involves culture of complementing Vero (CR2) cells, virus infection and manufacture, virus harvesting and subsequent downstream processing. The identification of suitable growth parameters for the complementing cell line and optimal limes for both infection and harvest are addressed. Various traditional harvest methods were investigated and found not to be suitable for a scaled up process. A method of harvesting, that exploits the elution of cell associated viruses by the competitive binding of exogenous heparin to virus envelope gC proteins, is described and is shown to yield significantly less contaminated process streams than sonication or osmotic approaches that involve cell rupture (with> 10-fold less complementing cell protein). High concentrations of salt (>0.8M NaCl) exhibit the same effect, although the high osmotic strength ruptures cells and increase the contamination of the process stream. This same heparin-gC protein affinity interaction is also shown to provide an efficient adsorptive purification procedure for herpes viruses which avoids the need to pre-treat the harvest material, apart from clarification, prior to chromatography. Subsequent column eluates provide product fractions with a 100-fold increase in virus titre and low levels of complementing cell protein and DNA (0.05 pg protein/pfu and 1.2 x 104 pg DNA/pfu respectively).

The development of heat recovery equipment from conception to commercialisation

A comprehensive survey of industrial sites and heat recovery products revealed gaps between equipment that was required and that which was available. Two heat recovery products were developed to fill those gaps: a gas-to-gas modular heat recovery unit; a gas-to-liquid exhaust gas heat exchanger. The former provided an entire heat recovery system in one unit. It was specifically designed to overcome the problems associated with existing component system of large design commitment, extensive installation and incompatibility between parts. The unit was intended to recover heat from multiple waste gas sources and, in particular, from baking ovens. A survey of the baking industry defined typical waste gas temperatures and flow rates, around which the unit was designed. The second unit was designed to recover heat from the exhaust gases of small diesel engines. The developed unit differed from existing designs by having a negligible effect on engine performance. In marketing terms these products are conceptual opposites. The first, a 'product-push' product generated from site and product surveys, required marketing following design. The second, a 'market-pull' product, resulted from a specific user need; this had a captive market and did not require marketing. Here marketing was replaced by commercial aspects including the protection of ideas, contracting, tendering and insurance requirements. These two product development routes are compared and contrasted. As a general conclusion this work suggests that it can be beneficial for small companies (as was the sponsor of this project) to undertake projects of the market-pull type. Generally they have a higher probability of success and are less capital intensive than their product-push counterparts. Development revealed shortcomings in three other fields: British Standards governing heat exchangers; financial assessment of energy saving schemes; degree day procedure of calculating energy savings. Methods are proposed to overcome these shortcomings.

DesaLink:solar powered desalination of brackish groundwater giving high output and high recovery

Desalination of groundwater is essential in many arid areas that are far from both seawater and fresh water resources. The ideal groundwater desalination system should operate using a sustainable energy source and provide high water output per land area and cost. To avoid discharging voluminous brine, it should also provide high recovery. To achieve these aims, we have designed DesaLink, a novel approach to linking the solar Rankine cycle to reverse osmosis (RO). To achieve high recovery without the need for multiple RO stages, DesaLink adopts a batch mode of operation. It is suited to use with a variety of solar thermal collectors including linear Fresnel reflectors (LFR). For example, using a LFR occupying 1,000m of land and providing steam at 200°C and 15.5 bar, DesaLink is predicted to provide 350m of fresh water per day at a recovery ratio of 0.7, when fed with brackish groundwater containing 5,000ppm of sodium chloride. Here, we report preliminary experiments to assess the feasibility of the concept. We study the effects of longitudinal dispersion, concentration polarisation and describe a pilot experiment to demonstrate the batch process using a materials testing machine. In addition, we demonstrate a prototype of DesaLink running from compressed air to simulate steam.