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).

Tsunami disaster recovery experience:a case study on micro, small and medium scale enterprises in Southern Sri Lanka

Post-disaster recovery of Micro, Small and Medium-Scale Enterprises (SMEs) remains an issue of interest for policy and practice given the wide scale occurrences of natural disasters around the globe and their significant impacts on local economies and SMEs. Asian Tsunami of December 2004 affected many SMEs in southern Sri Lanka. The study was developed to identify the main issues encountered by the Tsunami affected SMEs in Southern Sri Lanka in the process of their post-tsunami recovery. The study: a) identifies tsunami damage and loss in micro and SMEs in the Galle district; b) ascertains the type of benefits received from various parties by the affected micro and SMEs; c) evaluates the problems and difficulties faced by the beneficiary organizations in the benefit distribution process; and d) recommends strategies and policies for the tsunami-affected micro and SMEs for them to become self-sustaining within a reasonable time frame. Fifty randomly selected tsunami-affected micro and SMEs were surveyed for this study. Interviews were conducted in person with the business owners in order to identify the damages, recovery, rehabilitation, re-establishment and difficulties faced in the benefit distribution process. The analysis identifies that the benefits were given the wrong priorities and that they were not sufficient for the recovery process. In addition, the many governance-related problems that arose while distributing benefits are discussed. Overall, the business recovery rate was approximately 65%, and approximately 88% of business organizations were sole proprietorships. Therefore, the policies of the tsunami relief agencies should adequately address the needs of sole proprietorship business requirements. Consideration should also be given to strengthen the capacity and skills of the entrepreneurs by improving operational, technological, management and marketing skills and capabilities.