Polysaccharides vaccines

Many bacteria are surrounded by a polysaccharide capsule, which both provide antigens against which antibodies can act, the molecules that largely determine how virulent and pathogenic the organism and protects the main bacterial cell from the bodies defense systems.

It is relatively easy to create polysaccharide vaccines against the molecules in the capsule; but these molecules are often small, and not very immunogenic. As a consequence they:

§  Tend not to be effective in infants and young children (under 18-24 months);

§  Induce only short-term immunity - there is a slow immune response, with antibody levels rising slowly, with no immune memory.

Polysaccharide vaccines are a unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria. Pure polysaccharide vaccines available include: pneumococcal, meningococcal, and Salmonella typhi. The immune response to a pure polysaccharide vaccine is typically T-cell independent, which means that these vaccines are able to stimulate B-cells without the assistance of T-helper cells.

§  T-cell independent antigens, including polysaccharide vaccines, are not consistently immunogenic in children <2 years of age. Young children do not respond consistently to polysaccharide antigens, probably because of immaturity of the immune system.

§  Repeated doses of most inactivated protein vaccines cause the antibody titer to go progressively higher, or “boost.” Repeat doses of polysaccharide vaccines do not cause a booster response. This is not seen with polysaccharide antigens. Antibody induced with polysaccharide vaccines has less functional activity than that induced by protein antigens. This is because the predominant antibody produced in response to most polysaccharide vaccines is igm, and little igg is produced.

Polysaccharide vaccines only protect for a few years, and cannot be used in children under the age of abut 18 months. From this age their efficacy gradually increases. Group

C meningococcal vaccine, for example, is of comparable efficacy to the conjugate vaccine by the mid to late teens. In contrast to conjugate vaccines, polysaccharide vaccines induce antibody production, but do not induce a T-cell response. This means that they:

§  Do not induce immune memory..

§  May not prevent colonisation, e.g. Of the nasopharynx by meningococci. This means that, while they provide personal protection, they may not provide herd immunity - a person can still be colonised (infected but not ill), and pass a potentially pathogenic bug on to somebody else.

Because they are relatively simple to produce, they are also relatively cheap and uncomplicated.

For these reasons they are not generally suitable for universal use. Examples of polysaccharide vaccines which are, or have recently been used, include vaccines against:

·         Meningococcal disease caused by Neisseria meningitidis groups A, C, W135 and Y. Until the introduction of a group C conjugate vaccine a polysaccharide group c vaccine would be offered to contacts of cases of meningococcal disease

·         Pneumococcal vaccine. This is an interesting example, because there are also conjugate vaccines available or coming on to the market; but these protect against many fewer serotypes of disease than the 23-valent polysaccharide vaccine.

·         Haemophillus influenza type b (hib). Haemophilus influenzae type b (Hib). Haemophilus influenzae is a Gram-negative microorganism that is often found in the oropharynx of man. The majority of H. Influenzae strains are non-encapsulated, generally called non-typable H. Influenzae. However, some strains may be encapsulated.

Development of vaccine against N.MENINGITIDIS:

Host response:

Protection from meningococcal infection depends on innate immunity, in particular a functioning complement system; deficiencies of terminal complement components and alterations in complement regulators are both associated with an increased risk of infection. In addition, the humoral antibody response is essential for protection against the bacterium. The serum bactericidal antibody (SBA) assay measures killing of N. Meningitidis in the presence of specific antibodies that bind to the bacteria and activate complement.

 Capsular polysaccharide vaccines:

In the 1960s, the first successful vaccines were developed against groups A and C and were based on capsular polysaccharide. Subsequently, polysaccharide vaccines were introduced against groups W-135 and Y;, has over 85% efficacy against the A and C components in older children and adults. However, apart from the group A component, these vaccines are poorly immunogenic in children younger than 2 years of age. Furthermore, polysaccharides are T-cell–independent antigens that result in short lived immunity with no memory response. Thus, dosing is required every 3 to 5 years, but this may cause a reduced antibody response (hypo responsiveness) as compared with the response to initial vaccination, owing to a depleted memory B-cell pool.

Polysaccharide–Protein Conjugate Vaccines

To overcome the problem of short-lived protection against the meningococcus, covalent binding (conjugation) of polysaccharides to a protein carrier has been used, resulting in T-cell–dependent immunity and a memory response. In 1999, the United Kingdom became the first country to introduce the meningococcal group C polysaccharide–protein conjugate vaccine (menc) into schedules for routine infant immunization, with an initial catch-up campaign for children and adolescents up to 18 years of age. After the introduction of this vaccine, there was a marked decline in group C carriage and disease. Menc provides significant herd immunity, with a decline in disease even among unvaccinated persons, enagers, who constitute the main reservoir for meningococcal transmission.

Polysaccharide petide mimics

Another development of peptides vaccine strategy is the that mimic polysaccharide antigens. These peptides can be identified using anti-idiotypic antibodies or phage display libraries, and can mimic the immunological function of polysaccharides. The exact mechanisms responsible for this mimicry are yet unknown. Peptide mimics commonly contain a large number of hydrophobic amino acid residues, often with aromatic side chains. Based on these similarities, it is hypothesized that aromatic/aromatic and hydrophobic interactions are critical forces that modulate binding and that the basis of cross-reactivity is structural mimicry.

Concluding remarks:

Bacterial polysaccharides are the major surface components and immunity confers protection. The use of polysaccharides in vaccines has been partially successful, however, several problems remain to be solved. Pure polysaccharides are poor immunogens and most of them are TI antigens. Polysaccharide neoglycoconjugates as vaccines could be a way to convert a TI to TD antigen. Several examples are described with the Hib conjugate
vaccine as the best example. Peptide mimics of carbohydrate structures is a new an approach that may have good potential in the development of new vaccine.