Protective Activity of a Glycoconjugate Based on a Synthetic Hexasaccharide Related to a Fragment of Capsular Streptococcus Pneumoniae Serotype 14 Polysaccharide Chain

Abstract

We studied the effects of immunization with a conjugate of carrier protein and hexasaccharide ligand related to a fragment of capsular of Str. pneumoniae serotype 14 polysaccharide chain on activation of innate and adaptive immunity. It was found that two-fold immunization with the glycoconjugate adsorbed on aluminum hydroxide significantly increased the titer of IgG antibodies to capsular polysaccharide in the blood and protected 100% mice from infection with Str. pneumoniae serotype 14. Enhanced bactericidal activity of peripheral blood lymphocytes of mice was found 4 and 24 h after the first immunization with the immobilized glycoconjugate. Adsorption of the glycoconjugate on aluminum hydroxide resulted in modification of the immune processes at the stage of activation of innate immunity and subsequent strengthening of the adaptive immunity.

An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity

“…More than 90 different serotypes of S. pneumoniae have been identified based on the type of capsular polysaccharide (CPS) that they express . Among these, approximately 20 serotypes are the cause of 90 % pneumococcal diseases . The CPSs of pneumococcal serotypes are polymers comprised of multiple linear or branched RUs where, each RU consists of 2–8 monomers .…”

“…In addition to the semisynthetic vaccines, various synthetic approaches have been used to identify the effective immunogenic saccharide epitopes of the different pneumococcal serotypes to develop the third generation glycoconjugate vaccines . These studies revealed that conjugated short saccharide chains starting from di‐ to pentasaccharides (Figure ) that are equivalent or less than one or two RU derived from the CPS of S. pneumoniae serotypes 3, 6A, 6B, 14, 17S, 23F were able to provoke protective immune response in mice and rabbits and could be used as potential candidates to design specific glycoconjugate vaccines . A number of studies revealed that two epitopes, (1→3)‐ and (1→4)‐linked rhamnosyl‐ribitol, were the crucial epitopes (Figure b) and need to be included in oligosaccharide design to generate an effective glycoconjugate vaccine against the serotypes 6A, 6B, 6C and 6D .…”

The Effect of a BSA Conjugate of a Synthetic Hexasaccharide Related to the Fragment of Capsular Polysaccharide of Streptococcus pneumoniae Type 14 on the Activation of Innate and Adaptive Immune Responses

“…In the previous study, we revealed that sera obtained at 4 h after the single immunization of mice with GC without aluminum hydroxide did not possess bactericidal activity and those obtained at 24 h only weakly promoted phagocytosis of the live culture of heterologous pathogen ( Staphylococcus aureus ) by leukocytes. GC absorbed on aluminum hydroxide increased bactericidal activity of peripheral blood leukocytes of mice obtained at 4 h and more intensively at 24 h after the single immunization ( 39 ).…”

“…After the second immunization, the GC absorbed on aluminum hydroxide resulted in the formation of IgG antibodies to capsular PS. In the previous studies, it was shown that the hexasaccharide conjugate adsorbed on aluminum hydroxide protected immunized mice from S. pneumoniae serotype 14 ( 39 ). Without aluminum hydroxide, the GC did not possess the protective properties ( 39 ).…”

“…In the previous studies, it was shown that the hexasaccharide conjugate adsorbed on aluminum hydroxide protected immunized mice from S. pneumoniae serotype 14 ( 39 ). Without aluminum hydroxide, the GC did not possess the protective properties ( 39 ). In this period, against the background of normal CD4 + T helper cell numbers, the suppressor effect of CD8 + T lymphocytes decreased, the expression of the IL-2 receptor (CD25 + ) on T lymphocytes increased, the number of B lymphocytes increased, and the expression of MHC class II molecules on mononuclear leukocytes from the spleen increased.…”