Classes of Vaccines



The story of Edward Jenner is well known, although a form of vaccination deliberately transferring smallpox from pus or scabs was in use in China in the mid 16th century, or even much earlier, and arrived in Europe in the mid 1700’s.  This was the basis for Jenner’s discovery and an example of a live viral vaccine – smallpox is caused by an orthopox DNA virus, Variola, while the similar Vaccinia virus causes cowpox. In the past year, this story has come full circle because smallpox, having been eradicated in 1980, presents a potential to be used as a bioterrorism agent that has led to a need to manufacture and stockpile smallpox vaccines once again.

 











Two hundred years after Jenner, however, the complete genomes of both Variola and Vaccinia have been sequenced.  We know the structure of the proteins and other virus coat components and can potentially produce recombinant vaccines that are better characterized, produced more safely and easily and are also potentially easier to stockpile than the original viral vaccines. For the immediate needs, however, current smallpox vaccines, from a Vaccinia strain derived from the original skin-grown Dryvax, are grown in cell culture by Acambis and have less risk of side effects such as encephalitis. In Europe, Bavarian Nordic also produces cell-grown Vaccinia.

These viruses are attenuated. That is, their virulence is reduced by being passed many times through multiple cell culture cycles. In the case of mumps virus vaccine, attenuation is effected by passage through chick embryo cell culture. Other attenuated vaccines may have been chemically or physically treated. Killed and inactivated vaccines are similar; often formalin treated, but still have the effector mechanism of injection of a whole organism. Polio is an example of such a vaccine

Bacterial vaccines may be whole organism, such as another “old” vaccine – BCG – an attenuated Bacillus used for TB, but are more commonly antigen or subunit vaccines. Toxin-producing bacteria have vaccines developed from toxoids – modified toxins where the toxic effect is eliminated by modification of the protein – such as diphtheria. Vaccines against bacteraemic infections typically use a component of the bacterial cell -  wall protein or polysaccharide, for example meningitis vaccine.

Until the mid 1980s, these were essentially the only types of vaccines available and a wide selection of the worlds worst infectious diseases were largely covered. However, there were still large groups within the population that were left unprotected against relatively common diseases. In particular, young children could not be efficaciously vaccinated against common childhood complaints such as Haemophilus. This is because, although a vaccine was available, it relied on the development of an antigenic response to the bacterial cell wall polysaccharides. In older children and adults, the immune system is mature enough to develop a response to polysaccharides, which invoke a direct B-cell response, i.e. are T-cell independent, but in infants this is not the case.

Research on mechanism of action of the immune system led to the discovery that once a response was triggered, the T-cell dependent antibody response would generate antibodies to any foreign material associated with the principal trigger. Consequently, if the cell wall polysaccharides that you required an immune response against were linked to a suitable molecule that would develop a response, antibodies against both molecules would be produced. This is the basis of operation of the hugely successful conjugate vaccines that have revolutionized pediatric vaccination programs. A variety of these vaccines are now available, the first being Haemophilus influenzae B (meningitis) vaccines. In only three years, these new vaccines displaced the traditional polysaccharide vaccines.

Conjugation, linking two or more dissimilar molecules together by covalent bonding, is now being applied to a wide range of vaccines. Conjugate vaccines against multiple serotypes of pneumococcal infections are available, as well as against further types of Meningitis.

Conjugate vaccines also hold promise for emergent problems with old diseases. For example, the BCG vaccine for tuberculosis cannot be used in those immunosuppressed, for such as through HIV infection, because it is a whole, live, attenuated bacterial vaccine. However, a conjugate of a suitable toxoid with a tuberculosis cell wall saccharide could provide a relatively simple vaccine that would be stable, well characterized, able to be made in quantity and which could be effective in this target population.