Differences between polysaccharide and polysaccharide-protein conjugate vaccines

Differences between polysaccharide and polysaccharide-protein conjugate vaccines

Polysaccharides vaccines have been in use for the past thirty to forty years in order to prevent infections such as Streptococcus Pneumonia and Neisseria meningitis (caused by Haemophilus influenzae type b). However, these infections are one of the main causes of death and disease in children under five years old in certain geographical locations around the world (mainly developing countries) and the polysaccharide vaccine alone is not effective at treating these infections in children so young; thus the polysaccharide protein conjugate vaccine was developed.

The bacteria mentioned above are extracellular pathogens and are therefore enclosed in a capsule consisting of polysaccharides. This capsule is a major virulence determinant of the bacteria. So in order to protect ourselves from the infections caused by these bacteria, this capsule must be destroyed. These antibacterial polysaccharide vaccines are used to prevent bacterial infections caused by capsulated (extracellular) bacteria. Since they are vaccines, they contain part of the virulence determinant of the bacteria; in this case, the polysaccharide capsule in order to build up the individuals immunity/defence (by antibody production) against it. So, the polysaccharide vaccine can be described as an inactivated vaccine that contains fractions of the polysaccharide capsule of the bacteria, meaning that the bacteria has been inactivated using either heat or chemical such as formalin and is not active/alive and therefore cannot continue to grow or replicate once in the individual (as opposed to live attenuated vaccines); hence there is no risk of this type of vaccine causing any adverse effects to the individual (i.e. no risk of infection from the vaccine alone).

A polysaccharide vaccine can also be given as a pure vaccine, i.e. a vaccine that contains nothing but fractions of the polysaccharide capsule of the virulent bacteria (as opposed being mixed with other substances). If administered to the individual in this form, after inactivation of the bacteria, certain bacterial components, i.e. the polysaccharide capsule would need to be further purified for use in the vaccine.

These vaccine types would not be given to an individual in a single dose; rather multiple doses, each of which would affect the immune system in different ways. The first dose would have little or no effect in terms of immune response and antibody production, and serves to get the immune system ready for further exposure to the bacteria, after which further doses would be administered which would then elicit a protective immune response and the production of antibodies. These response by the immune system can be described as humoral. Humoral action depends primarily on protein action (antibody proteins) which are produced by B cells and is only effective against extracellular capsulated pathogens (are specific to antigens, containing receptors for specification). ‘Antibody titres against inactivated antigens diminish with time. As a result, these polysaccharide vaccine may in some instances require periodic supplemental doses to increase, or boost antibody titres'[i] within the body.

In normal circumstances, if the body was to encounter these bacterium, the usual course of defence would be ‘the activation of part of the innate immune system called the complement system of the host which would serve to ‘complement’/aid the antibodies produced by the B lymphocytes in getting rid of these pathogens from the body'[ii] (so the innate immune system is the bodies first line of defence; if this system fails to get rid of the pathogenic microbes, then the adaptive immune system is activate, Humoral or cell mediated). The polysaccharide capsule of the bacteria would be presented to the B cells indirectly via antigen-presenting cells (serum anti-polysaccharide[iii]). This would activate CD4+ T cells which would serve to ‘enhance the affinity of antibody binding on subsequent exposure to the specific antigen. However for children, the capsule would be presented directly to the B lymphocyte cells surface and not indirectly via a polysaccharide antigen, meaning that the CD4 + T cells would not be activated, resulting in a weak proliferation of the B cells to produce IgM and IgG2 without forming memory cells.'[iv] These B memory cells are important in that they help to protect the body in the event of it being re-exposed to the antigen; they last for many years and circulate in the blood (can also be found in bone) and begin to produce antibodies if an antigen is detected (Vaccines are able to provide a link between memory and specificity). Therefore B memory cells are of vital importance, especially to young children who may not have been vaccinated against the certain bacterial infection as of yet. So in young children, innate immune system and B lymphocyte activity is weak (as babies in the mother’s womb, the child would have been reliant upon it’s mother for protection, however when born, the child would be producing antibodies for the first time and would therefore be doing so at a much slower rate than adults; vaccinations would speed up this process of natural immunity of bacterial infection resistance) however if produced and these bacterium are encountered, the next steps would be as mentioned above). [v]

Polysaccharides vaccines are however still useful as strong immunising agents. Depending on the age and health of the individual (more effective in adults, as described above), one dose of the vaccine is sufficient to elicit a maximal antibody response, which would serve to increase the individuals antibody concentration lasting for a long time, thus enabling the individual to build up their natural immunity to that particular bacterial infection. However, the response to children is limited in terms of their antibody production and largely depends on the age at which they were first vaccinated. The response of children to the polysaccharide vaccine would vary from child to child; it may elicit a slight increase in antibody production or may have no effect at all .This however, is most probably due the lack of development of the child’s immune system. The vaccine, in some cases, may also have no effect and be poor immunizing agents in certain adults. The reasons as to why there are these limitation to the vaccines in certain individuals is not yet well understood. ‘A predominant stimulation of suppressor cells is one possibility, antigenic relatedness to polysaccharide structures in the human tissues causing immunological tolerance is another one, however more research is still needed to be carried out on this matter’.[vi] The poor response of children to the polysaccharide vaccine also limits where it is used around the world; the use of the polysaccharide vaccine is often limited to western countries or developed countries, as the bacterial diseases such as Pneumoniae are one of the main causes of death and ill health in young children in developing countries. This poses a problem, as the number of children affected by these bacterial infections in developing countries far outweigh the number of children affected in developed countries, and so if the vaccine is in most cases ineffective at preventing/treating these infections in these young children it means that they would remain untreated/not immunised against the bacterial infections and it is likely that if they catch the bacterial infection in the future, they might succumbed to it due to lack of an immune response the bacteria (lack of specific antibodies).

It is due to these limitations in the polysaccharide vaccines, the inconsistent responses of children to polysaccharide antigens and the differences between adult and child defence mechanisms and actions in response to these bacterium that led to the development of polysaccharide-protein conjugate vaccines.

As described previously, both polysaccharide and polysaccharide – protein conjugate vaccines can be classified as inactivated vaccines which are composed of certain parts (the virulence determinants) of the bacteria. These types of inactivated vaccines may be protein or polysaccharide based. ‘Protein-based vaccines may include toxoids ( which is a form of inactivated bacterial toxin) and subunit or subvirion products. The majority of polysaccharide-based vaccines consist of pure cell wall polysaccharide from bacteria. Conjugate polysaccharide vaccines on the other hand contain polysaccharide that is chemically linked to this protein carrier (may be diptheria toxoid), which serves to improve the immuogenecisity of the polysaccharide. This linkage makes the polysaccharide a much more potent vaccine'[vii], which is why the polysaccharide- protein conjugate vaccine is much more widely used, as it elicits greater effects in terms of immunity to the bacterial infection and has far fewer limitations in its actions than the polysaccharide vaccine alone meaning the vaccine can be given and would have an effect on a much wider range of individuals, i.e. can be used as an immunising agent for young children for which these bacteria are most likely to cause infection (either on its own or in combination with other vaccines/medicines) which if untreated/not immunised, may progress to mortality.

The polysaccharide – protein conjugate vaccine proves to be effective primarily due to the role of the carrier protein which is conjugated to the polysaccharide, as this ensures that T cells (or T- helper lymphocytes) are involved in the activation of B cells which then go on to produce the antibody proteins that are required for immune protection again these pathogenic extracellular bacterial types (the mechanisms of the B cells are described previously in this essay). Below, figure 1 demonstrates how the polysaccharide vaccine and the polysaccharide – protein conjugate vaccine differ in their effects at eliciting certain immune responses in different individuals;

 

http://www.springerprotocols.com/Abstract/doi/10.1385/1-59259-399-2:153#CR3

Figure 1 showing the antibody production in response to both the polysaccharide vaccine and the polysaccharide- protein conjugate vaccine

 

 

 

 

Figure 1 demonstrates that if using the polysaccharide vaccine, the polysaccharide alone does not prove to be that effective in activating the B cells and thus producing antibodies in young children of under two years old. In some cases, if antibodies are formed, they would be of short duration and would not last long in the blood, bone or marrow (i.e. activation/formation of B memory cells would not occur which would reduce the child’s risk of fighting off the infection if re-exposed to the bacteria – as described previously in this essay). On the other hand, the carrier protein in the polysaccharide- protein conjugate vaccines elicit the aid of T-cells to help in the activation of B-cells. ‘It is thought that the conjugate is taken up by polysaccharide-specific B-cells, processed, and presented to carrier-specific T-cells. The involvement of T-cells results in the activation of B-cells to production of antibodies and induction of the important B memory cells in children younger than 2 yr of age, ‘[viii]hence the conjugate vaccine is more effective for use in very young children.

 

 

 

[i] http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/prinvac.pdf

[ii] (Siegrist CA. Immunological requirements for vaccines to be used in early life. In: Bloomw BR, Paul-Henri, editors. The vaccine book. USA: California Elsevier Science; 2003)

[iii] http://link.springer.com/article/10.1007%2FBF01641750#page-1

[iv] Seder RA, Mascola JR. A basic immunology of vaccine development. In: Bloom BR, Paul-Henri, editors. The vaccine book. USA: California Elsevier Science; 2003.

[v] (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361805/)

[vi] http://link.springer.com/article/10.1007%2FBF01641750#page-1

[vii] http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/prinvac.pdf

[viii] http://www.springerprotocols.com/Abstract/doi/10.1385/1-59259-399-2:153#CR3

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