Saar Kuzi
Alessandra Coutinho Fernandes
William Cope
Richard Tapping
Kashif Ahmad
Reda Sadki
Shubhra Kanti Karmaker Santu
Adam P Rusch
Elle Meisner
Nereyda Ochoa
Landon J. Kunzelman
James DotimasFA16 Immunization Module’s Updates
Why Polysaccharide Vaccines Are Less Effective than Conjugates
I thought this may have been a slightly difficult concept that was presented, so I wanted to elaborate more here.
Polysaccharide vaccines are not as effective as live attenuated vaccines and inactivated vaccines that are based on protein. The reason for this is because B-Cells can only truly undergo isotype switching, robust affinity maturation, and extensive proliferation in the presence of activated T-helper cells.
T-helper cell activation specifically requires protein antigen presentation via the MHCII-peptide complexes of professional antigen presenting cells. Once the T-cells have been appropriately activated by antigen presenting cells, they can then activate B-cells by interacting with B-cell MHCII-peptide complexes. This interaction between T-cells and B-cells via a protein antigen is what creates a robust B-cell response.
Polysaccharide vaccines contain only the polysaccharides of the surface capsules of bacteria. These polysaccharides cannot be presented by B-cell MHCII molecules and a result is that there is no activation of B-cells by T-helper cells. B-cells alone are able to recognize these polysaccharides and respond to them, however their response to polysaccharides without T-cell help is not very robust: only low affinity IgM is created (with very little IgG), and low levels of B-cell proliferation occurs.
Currently available polysaccharide vaccines include pneumococcal, meningococcal, and typhoid Vi. Typically these vaccines are not effective for use in children younger than 2 years of age, as these children do not receive the T-cell help they need to generate a robust immune response due to an immature immune system.
A better alternative to polysaccharide vaccines is protein-conjugated, or conjugate vaccines for short. The polysaccharide recognized by B-Cells is linked to another protein antigen that is able to be processed and recognized by T-helper cells. B-cells will recognize the polysaccharide moiety linked to the protein antigen, phagocytize the protein-linked polysaccharide, and then present the processed peptide on their MHCII complexes. The processing and presentation of the conjugated protein antigen on B-Cell MHCII complexes allows for those B-cells to be recognized and receive help from T-cells. The result is the proliferation of that B-cell that is specific to that polysaccharide.
The below image is an example of how a B-cell can recognize a specific polysacharride moeity, but still recieve T-cell help by presenting the processed protein part of the conjugated vaccine. I hope this helps explain a more difficult concept.
To learn more about this process please consult the following 4 links/ resources which were helpful in my understanding of conjugated vaccines:
Nice synopsis. The diagram is very useful especially if you understand the order of the events presented.
@Nicholas Romito. This is by far one of the most interesting topics I learned in immunology. I also read about the conjugate vaccines and think that it is amazing how the immune response can be large amplified by addition of the peptide fragments to create a stronger and longer protection against foreign organisms. Your diagram made it very clear on the mechanism and how vaccines can stimulate our immune system to do such an excellent jobs in combating micro-organisms.
When we first learned about it, I thought it was a fascinating concept that the B-cell had the ability to turn something that originally isn't detectable to something instantly recognized by an appropriate T-cell. I do wonder whether upcoming innovations would include a related concept that may be beneficial to immature immune systems such as that of children less than 2 years of age.