190
disaccharide in which O-3, O-3′, O-4′, C 2 -N and C 2 -N′ are acylated with different C:12 and C:14 fatty acids. The lipid A confers the toxicity to the LPS. In addition, it has to be noted that the O -specific oligosaccharide that corresponds to a
sequence of oligosaccharide units is unique for each bacterial serotype and provides
an immunological property to the bacteria. As a result, several studies involving different moieties of lipopolysaccharides were carried out for the development of vaccines and drugs [31, 33, 34].
11.7.3 LPS-Derived Vaccines or
LPS-Protein Neoglycoconjugates
Various studies were carried out on the use of LPS derivatives as vaccines. It was
found that the immune reaction relies mainly on the LPS, and it has been efficiently
utilized for vaccination. However, the use of the LPS alone for vaccination is not
efficient, as, because of its small size, it is not recognized by the immune system as
it has resistance to non-specific host immunity such as complement system and
resistance to specific host immunity (poor antibody response) [35, 36].
However, when conjugated to a protein carrier, the LPS is able to induce an
immunological reaction and an extended immunity. Landsteiner’s group was the
first to utilize carbohydrate-protein conjugates as immunogens [37, 38], and lately,
it was discovered that they could induce a strong antibody reaction [39]. Landsteiner’s
group was also first to refer to the carbohydrate-protein conjugate as a hapten
[37, 38].
Figure 11.2 is representing the immune response generated by oligosaccharide
antigen-carrier protein vaccines [40]. The interaction of the glycoconjugate vaccine
(Fig. 11.2) with the B cell receptor (BCR) stimulates the lymphocytes and results in
the activation of plasma B cells to secrete immunoglobulins, while the neoglycoconjugate vaccine is recognized by the polysaccharide specific B cell receptors. The
carrier protein will enter the B cell by phagocytosis. Then, the degradation of the
protein carrier in B cells will be done by lysosomal enzymes into short peptides
called epitopes. At that time these epitopes will be recruited by a special protein
called major histocompatibility protein II (MHC II) that are presented at the cell
surface of antigen-presenting cell (APC) or B cell and interact with the carrierpeptide- specific T cells (helper T cell) which send a signal to produce polysaccharide specific plasma cells and polysaccharide specific memory B cells [40].
The synthesis of efficient glycoconjugate vaccines has been challenging, since
their efficacy relies on different factors, such as the saccharide size, the average
number of saccharide chains per conjugate molecule, the nature of the carrier and
the distance between the saccharide and the protein in the formed glycoconjugate
(Fig. 11.3) [41–44].
M. Bologna et al.
disaccharide in which O-3, O-3′, O-4′, C 2 -N and C 2 -N′ are acylated with different C:12 and C:14 fatty acids. The lipid A confers the toxicity to the LPS. In addition, it has to be noted that the O -specific oligosaccharide that corresponds to a
sequence of oligosaccharide units is unique for each bacterial serotype and provides
an immunological property to the bacteria. As a result, several studies involving different moieties of lipopolysaccharides were carried out for the development of vaccines and drugs [31, 33, 34].
11.7.3 LPS-Derived Vaccines or
LPS-Protein Neoglycoconjugates
Various studies were carried out on the use of LPS derivatives as vaccines. It was
found that the immune reaction relies mainly on the LPS, and it has been efficiently
utilized for vaccination. However, the use of the LPS alone for vaccination is not
efficient, as, because of its small size, it is not recognized by the immune system as
it has resistance to non-specific host immunity such as complement system and
resistance to specific host immunity (poor antibody response) [35, 36].
However, when conjugated to a protein carrier, the LPS is able to induce an
immunological reaction and an extended immunity. Landsteiner’s group was the
first to utilize carbohydrate-protein conjugates as immunogens [37, 38], and lately,
it was discovered that they could induce a strong antibody reaction [39]. Landsteiner’s
group was also first to refer to the carbohydrate-protein conjugate as a hapten
[37, 38].
Figure 11.2 is representing the immune response generated by oligosaccharide
antigen-carrier protein vaccines [40]. The interaction of the glycoconjugate vaccine
(Fig. 11.2) with the B cell receptor (BCR) stimulates the lymphocytes and results in
the activation of plasma B cells to secrete immunoglobulins, while the neoglycoconjugate vaccine is recognized by the polysaccharide specific B cell receptors. The
carrier protein will enter the B cell by phagocytosis. Then, the degradation of the
protein carrier in B cells will be done by lysosomal enzymes into short peptides
called epitopes. At that time these epitopes will be recruited by a special protein
called major histocompatibility protein II (MHC II) that are presented at the cell
surface of antigen-presenting cell (APC) or B cell and interact with the carrierpeptide- specific T cells (helper T cell) which send a signal to produce polysaccharide specific plasma cells and polysaccharide specific memory B cells [40].
The synthesis of efficient glycoconjugate vaccines has been challenging, since
their efficacy relies on different factors, such as the saccharide size, the average
number of saccharide chains per conjugate molecule, the nature of the carrier and
the distance between the saccharide and the protein in the formed glycoconjugate
(Fig. 11.3) [41–44].
M. Bologna et al.