Group B Streptococcus Vaccines

Bacterial infections can have serious consequences, especially in infants whose immune system is not yet mature and in older adults with reduced immune function, and group B Streptococcus is a prominent representative of such bacteria. Vaccine is one of the most cost-effective strategies for preventing bacterial infections. Creative Biolabs has deep research on the pathogenesis of bacteria and its interaction with the host and has made numerous attempts in bacterial vaccines. We have accumulated a wealth of experience and developed a number of high-quality products so can help you successfully complete the development of GBS vaccine.

Group B Streptococcus

Group B streptococcus (GBS) is a major cause of severe infections in the elderly and invasive diseases in newborns. GBS is also known as Streptococcus agalactiae, a gram-positive opportunistic pathogen that colonizes the genitourinary and gastrointestinal tract of approximately 50% of healthy adults. According to the age at which the infant develops symptoms after GBS infection, such GBS infection can be divided into early-onset disease (EOD) and late-onset disease (LOD), and the prerequisite of EOD is the colonization of bacteria in the mother. The disease usually occurs within a few hours to a few days after infection, and the condition rapidly develops from pneumonia and respiratory failure to bacteremia and septic shock. The LOD is manifested as a blood infection and has a high probability of developing into meningitis. Immunocompromised, patients with malignant tumor, those with metabolic diseases like diabetes, and the elderly are at high risk of GBS infection. In the United States, approximately 15% of people die from GBS infection. The recent discovery that some of the new GBS strains are resistant to erythromycin, clindamycin, and penicillin makes the treatment of GBS a thorny issue.

Pathogenicity of Group B Streptococcus

GBS is capable of encoding a variety of transcriptional regulators as well as virulence factors to accommodate the host's immune response and cause disease. Pore-forming toxins are important components of bacterial disease virulence factors that help bacteria enter host cells and survive intracellularly and spread to other parts of the body. GBS encodes two pore-forming toxins, Christie Atkins Munch Peterson (CAMP) and β-hemolysin/cytolysin (β-H/C). β-H/C can promote GBS invasion of epithelial cells in the lungs and break through the blood-brain barrier. It can also impair heart function and lead to liver failure as well as stimulate the host's inflammatory response contributing to neurological sequelae. CAMP factor is a protein secreted by GBS. Studies on CAMP factor have shown that partially purified CAMP factor can cause death in rabbits.

In addition to secreting pore-forming toxins, GBS can also encode a range of factors to evade host immune surveillance. The GBS surface-coated capsular polysaccharide (CPS) is rich in sialic acid, which is also present in the glycan of vertebrate cells. This molecular simulation makes the host cell unable to recognize GBS, so CPS can protect GBS from the host's complement factor C3 deposition and phagocytosis. CPS has also become one of the targets of the GBS vaccine because of its importance in pathogenicity. SodA is a superoxide dismutase encoded by GBS that works synergistically with Mn²⁺. One of the mechanisms by which GBS evades host immune responses is its resistance to host ROS. Furthermore, C5a peptidase, serine protease, resistance to host antimicrobial peptides, penicillin-binding protein, changes in surface charge of the cells of GBS, and pili can help GBS escape the host's immune response. The current research has also found many factors related to the adhesion of GBS to host cell surface and invading cells, including fibrinogen-binding proteins, laminin-binding proteins, serine-rich repeat proteins, and αC proteins. Moreover, the lysis of hyaluronate by GBS and the uptake of methionine are also responsible for its pathogenicity.

Fig.1 Regulation of factors important for Group B Streptococci disease pathogenesis. (Rajagopal L, 2009)

Development of the Group B Streptococcus Vaccines

CPS as a GBS immune escape mechanism is considered to be an ideal candidate for GBS vaccine. However, previous studies have shown that CPS immunization alone does not provide sufficient protection, and GBS polysaccharide conjugate vaccine (PCV) is capable of inducing strong and high levels of CPS-specific antibody responses. Clinical trials of trivalent CRM₁₉₇ conjugate vaccines have shown that pregnant women vaccinated with this vaccine are able to produce sufficient CPS-specific antibodies and that this antibody can pass through the placental barrier to protect infants. Another clinical trial of pentavalent GBS PCV also showed good efficacy.

Although such PCV vaccines have good results, their immune interference with other similar conjugate vaccines may cause problems. Therefore, protein antigens that are structurally conserved and capable of inducing a strong immune response against most GBS strains have become hot spots in the development of GBS vaccines. A protein vaccine that fuses the highly antigenic N-terminus of αC and Rib, GBS-NN, showed good results in clinical trials. A conserved region of GBS pilin protein identified by scientists can also induce immune responses against different serotypes of GBS. Other GBS surface proteins are also in the preclinical evaluation stage as a spectrum vaccine.

Creative Biolabs is an expert in the field of vaccines, with a group of scientists from around the world forming a professional research team. In the development of more than ten years, we have delivered a large number of vaccine products and services to researchers all over the world, and have won unanimous praise from customers. Any of your needs are the driving force behind our tireless progress.

Reference

1. Rajagopal L. (2009). “Understanding the regulation of Group B Streptococcal virulence factors”. Future Microbiol. 4(2), 201-21.

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.