Close

Tell a friend

Your name: Your Email: Your friend's name: Your friend's Email:

Link: Comment:

Vaccine Development

Tasks

The key working tasks of the department are:

• Improvement of manufacturing processes for well-known vaccines with special importance on eliminating unwished ingredients and improving output
• Development of manufacturing processes and formulation of new biological products and manufacturing of them to clinical studies
• Transfer of technology both externally and internally
• Development of new combine vaccines from well-known vaccines by combining and/or clinically documenting new applications
• Clinical documentation of both new as well as existing biological products

Production Support

SSI is committed to eliminate use of all unnecessary ingredients from their vaccine manufacturing processes and final products and to improve the yield of the different production processes.

Process Development for New Vaccine Candidates

SSI has the capability of using a number of expression systems and pilot scale facilities to provide GMP manufactured batches for clinical trials.

The antigens are produced in GMP pilot plant facilities using expression systems that aim to minimize the amount of additional sequences such as Tags. The fermentation and down stream processes are developed using raw materials which are free from sources of animal or human origin.

The development of scalable API production processes is made in close co-operation with formulation chemists so that an API can be further processed to the final product.

Combination Vaccines

Combination vaccines manufactured at SSI contain from one to four of the components; diphtheria vaccine (D), tetanus vaccine (T), acellular pertussis vaccine (aP) and inactivated poliovirus vaccine (IPV), which in varying combinations are marketed vaccines both in Denmark and abroad.

The clinical development of combination vaccines in Department of Vaccine Development includes clinical trials to obtain new indications or new markets or if the production method for a vaccine is changed.

Adjuvant/formulation development

Adjuvants, which in latin means ”to help”, have been used to enhance the immune response in vaccines since the early 1920s. Most vaccines in development today are based on the subunit technology, where one or more recombinant antigens are mixed with an appropriate adjuvant. Subunit vaccines are well defined products where the side effects are minimised compared to a whole cell vaccine.

Many subunit vaccines do not induce an adequate immune response compared to the original whole cell vaccines and may not induce a sufficient protection level. This is why there is a special need for adjuvants for subunit vaccines. Adjuvants are used to increase the potency of antigenically weak peptides in subunit vaccines, to modulate the antibody subclasses (Th1/Th2), enhance the persistence of the immune response and to increase the immune response in immunosuppressed individuals. At the same time the amount of antigen in the vaccine can be reduced, thus reducing the cost of the vaccine for the patient. The lower amount of antigen also decreases the likelihood of antigen competition in combination vaccines where high antigen content can result in a lower protection level for one or more of the antigens.

The Vaccine Development Department is developing both adjuvant systems owned by SSI and adjuvant systems from external partners.

Correct formulations of vaccines are important to achieve long product stability. The formulated product can either be lyophilised or stored at a certain temperature, typically cool or frozen storage. The formulations are characterised physically and chemically. Stability studies are carried out and an optimal formulation is selected.

The Vaccine Development Department is developing chemical analyses as well as immunological analyses for specific model vaccines.

Tuberculosis Vaccine Development

SSI co-operates with several international organisations and companies on developing new vaccines against TB. One of the vaccine candidates, a fusion protein containing two proteins, Ag85B and ESAT-6, has repeatedly shown to been a very effective vaccine against infection with M. tuberculosis in many different animal models.

The Vaccine Development Department has developed and implemented GMP pilot scala production process and analysis for characterization and release of the product.

The vaccine has been used in several clinical trials and has shown promising safety and immunogenic data.

Skin Testing for Detection of Tuberculosis Infection

Tuberculin PPD, which is a complex mixture of many different antigens from Mycobacterium tuberculosis, has been used for 100 years for the detection of tuberculosis infection by skin testing (Mantoux). In case of an infection a localized redness and swelling is seen at the injection site 2-3 days after testing. The reaction is seen in persons with active tuberculosis, but it also appears in latent infected, with no signs of disease. However, PPD may also induce a skin reaction in healthy individuals sensitized by previous BCG vaccination or by contact with avirulent, environmental mycobacteria. It is possible to compensate for a non-specific reaction by using different cut-off values for the reaction size based on knowledge of a person's vaccination status and habitat. However, a biological variation from person to person should be taken into consideration besides a possibility of a reduced immune response in immune compromised individuals co-infected with HIV. From the above it is clear that there is a strong need for a more specific agent with a well defined cut-off limit giving a skin reaction only in true cases of a tuberculosis infection.

At Statens Serum Institut a series of tuberculosis specific antigens have been identified of which two have been applied in a new skin test agent called C-TB

The preliminary results of clinical trials have shown that C-TB is a safe agent in humans, that there is no reaction in healthy, BCG vaccinated humans and reactions in former Tuberculosis infected humans.