The Importance of Group B Streptococcus (GBS) Vaccine Development

The gastrointestinal and vaginal epithelium of a substantial proportion of robust women are the host for GBS. GBS is a pathogenic bacterium that results in adhering and potentially ascending intrauterine infection. GBS is the main reason that causes invasive infections for newborns, pregnant women, and the old. There are capsular polysaccharides (PS) on the GBS strain surface, which are major virulence factors. Ten different PS serotypes have been identified. Neonates are easily infected with GBS from the maternal genital tract which may cause newborn bacteremia, prematurity, and meningitis. It is the potential to prepare conjugates by using pilus proteins and surface glycan antigens because they may extend vaccine coverage. It is the best tactic for pregnant women to vaccinate to prevent GBS infection in newborns.

Fig.1 GBS virulence factors with their specific targets and mechanisms. (Liu & Liu, 2022)

GBS Pilus Protein Conjugation Services at CD BioGlyco

There are three independent loci on GBS, pilus island 1 (PI-1), pilus island 2a (PI-2a), and pilus island 2b (PI-2b). GBS80 pilus protein is the primary component of GBS PI-1 pilus. CD BioGlyco utilizes the GBS80 to be a carrier to conjugate with GBS polysaccharide II to develop the GBS conjugate vaccine. Because linking GBS polysaccharide II to the GBS80 pilus protein has the potential to broaden the coverage range of the vaccine. GBS80 pilus protein is composed of three domains: N1, N2, and N3. The N2 and N3 domains are made up of 35 kDa C-terminal fragments. Polysaccharide II is a large and complex negatively charged polymer, whose repeating unit is illustrated in Fig.2.

Fig.2 The repeating unit of GBS polysaccharide II. (CD BioGlyco)

Currently, CD BioGlyco utilizes a highly effective approach in the preparation of glycoconjugate vaccines. We attach alkyne-containing bifunctional linkers onto carrier protein tyrosine residues. Then we utilize copper-mediated azide-alkyne [3+2] cycloaddition to condense glycans. This biphasic tyrosine conjugation technique facilitates the rapid identification of specific sites for glycan attachment by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analysis. Our method produces a more consistent batch-to-batch production process compared to traditional random conjugation. Additionally, the dual-step process ensures the preservation of protective protein epitopes. Our method allows for quick in vitro assessment of the retention of immunogenic epitopes on tyrosine-modified proteins before glycan conjugation. Subsequently, we quantify total saccharides by high-performance anion-exchange chromatography/pulsed amperometric detection (HPAEC-PAD).

Fig.3 Conjugation of polysaccharide II with GBS80. (CD BioGlyco)

Advantages of Us

• Our GBS carrier conjugation method affords a conjugate with a higher coupling efficiency.
• Our GBS carrier displays properties that are comparable to Cross-reacting Material 197 (CRM197), a protein commonly used in commercial vaccines.
• Our conjugation technique enables precise control of the conjugation chemistry.
• Our conjugation technique improves the analytical characterization of glycan-protein vaccines.
• Our conjugation technique determines the relationship between their immunological activity and specific attachment sites.

CD BioGlyco is a leading glycobiology company with years of experience and advanced technologies. Our core business includes Carbohydrate-based Vaccine Development which is based on our Glyco™ Vaccine Development Platform, a unique technology platform. If you are interested in our services, please feel free to contact us for more detailed information.

References:

1. Liu, Y.; Liu, J. Group B streptococcus: virulence factors and pathogenic mechanism. Microorganisms. 2022, 10: 2483.
2. Micoli, F.; et al. Protein carriers for glycoconjugate vaccines: history, selection criteria, characterization, and new trends. Molecules. 2018, 23(6): 1451.