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Streptococcus agalactiae is the only species of the Lancefield group, that is, group B streptococcus (GBS). It is therefore sometimes simply referred to as GBS. It is a gram-positive coccus and a commensal bacterium of the human gastrointestinal and genitourinary tracts. It is an opportunistic pathogen that can cause invasive disease and life-threatening infections, most often in the elderly, the immunocompromised and newborns. GBS is a significant cause of neonatal morbidity and mortality.
GBS colonization in pregnant women is mostly asymptomatic, which is the reservoir of the infection in the following pregnancy. It is one of the most significant uropathogens responsible for UTI, IAI, postpartum endometritis, and postpartum sepsis in pregnancy. Even more seriously, it may ascend to the uterus and cause chorioamnionitis. It can trigger PROM and preterm birth and results in a high EOD risk for newborns. For newborns, GBS infection is one of the most severe problems in the early stage of their lives. In newborns, GBSD can be divided into two types: early-onset disease (EOD) which develops within 1 week of age, and disease that appears after 1 week of age but before 3 months of age is defined as late-onset disease (LOD). In early-onset GBS disease of newborns, the majority of cases are acquired from colonized mothers either by ascending infection or during vaginal delivery. Late-onset sepsis, however, is thought to be acquired from hospital or community sources. Early-onset disease, on the other hand, has an acute fulminant onset, generally presenting within hours to days of birth with non-specific respiratory distress, somnolence, and fluctuating blood pressure. It rapidly progresses to fulminant sepsis and pneumonia. High mortality and long-term sequelae such as developmental delay, hearing and vision loss, and cerebral palsy remain a significant issue among survivors. In contrast, late-onset disease often has an insidious onset with bacteremia. It is also more likely to be complicated by purulent meningitis, which places affected individuals at higher risk for developing neurological deficits, resulting in a heavy long-term burden for patients' families and the larger community. As a result, preventative strategies against this particular population have always been a major research focus in GBS.
Figure 1. Ascending GBS Infection
(Source: Vornhagen J, et al. 2017)
To address this issue, most countries have implemented universal screening for women in the third trimester of pregnancy and administer intrapartum antibiotic prophylaxis (IAP) to those at high risk or with GBS colonization. The current primary method involves collecting vaginal and rectal swabs for bacterial culture at 35–37 weeks of gestation, with molecular diagnostic techniques also being applied. Although this strategy has significantly reduced the incidence of EOD, a key limitation is that it has no preventive effect against LOD. Existing screening results typically only provide a qualitative "yes or no" outcome, failing to fully utilize the potential of the samples. If the isolated strains could be further analyzed using phenotypic and molecular detection techniques (such as serotyping and virulence gene identification), it would greatly enhance our understanding of GBS epidemiology.
Maternal vaccination against GBS is considered the most effective method for preventing GBS disease. Vaccinating mothers during pregnancy would transfer antibodies from mother to fetus across the placenta. Maternal antibodies would passively protect the newborn from GBS while the infant's own immune system develops and it is at the greatest risk for infection. This approach targets prevention of early-onset and late-onset disease in infants and possibly also GBS-associated stillbirth and maternal GBS infection. The two main research areas on GBS vaccines are capsular polysaccharide conjugate vaccines and surface protein vaccines. Capsular polysaccharide conjugate vaccines are the most advanced vaccine candidate and strategy, as analogous pneumococcal and Haemophilus influenzae type b conjugate vaccines have already been successfully developed and implemented. This approach conjugates the capsular polysaccharides of the most prevalent circulating GBS serotypes to carrier proteins to elicit strong functional antibodies. Early clinical trials of mono- and bivalent capsular polysaccharide conjugate vaccines using tetanus toxoid as a carrier protein demonstrated that they were safe and well-tolerated. Several multivalent conjugate vaccines against multiple serotypes are now in phase III clinical trials with encouraging safety and immunogenicity results. These studies should provide the final data for approval of the vaccines over the next few years. A second approach to vaccine development is based on GBS surface-conserved proteins. The main benefit of a vaccine of this type would be that it would not be subject to the constraints of serotype specificity, offering a more universal protection and would be less likely to be subject to "serotype replacement". A number of promising protein antigens are currently in preclinical or early clinical stage development. Although the future of GBS vaccine development looks promising, there are a number of outstanding issues, including the identification of the optimal vaccine formulation (number of serotypes included in the vaccine), the evaluation of vaccine efficacy in different geographical regions and in different population, and the availability and affordability of the vaccine worldwide.
Figure 2. S. agalactiae vaccines
(Source: Pena JMS, et al. 2024)
Beyond traditional capsular polysaccharide and protein vaccines, researchers have developed several novel strategies for Streptococcus agalactiae vaccine development. The Srr1 and Srr2 proteins on the surface of Streptococcus agalactiae help the bacteria infect and colonize through a "latch" mechanism. Scientists have used this "latch" portion to create a vaccine, which has shown broad-spectrum protection in mouse experiments—meaning it was effective against all tested Streptococcus agalactiae strains, regardless of their serotype. The C5a peptidase is a key virulence factor of the bacteria. Encapsulating it in specialized microspheres and injecting it into mice caused a full immune response and enabled mice to fight off attacks by multiple different serotypes of Streptococcus agalactiae. Also, because pili enable bacteria to adhere to host tissues, vaccines based on pili may also cause antibodies to form that are able to prevent Streptococcus agalactiae from colonizing. Vaccines based on pili could prevent infection and provide cross-protection by causing the body to mount an immune response against multiple different Streptococcus agalactiae serotypes. However, due to antigenic variation, not all protective pilin protein subunits could be included in a vaccine. Another vaccine approach involves conjugating capsular polysaccharides to protein nanoparticles or virus-like particles. This method "decorates" the bacterial capsular polysaccharides onto tiny, virus-like particles. This structure can significantly enhance the immune system's recognition and response. Research has demonstrated that this "glyconanoparticle" vaccine could trigger a strong immune response with a single dose in mice, providing optimism in the development of a "one-shot" Streptococcus agalactiae vaccine.
The main objective of the currently tested Streptococcus agalactiae vaccines is to generate specific IgG antibodies that will clear the bacteria by opsonophagocytic killing. A large body of research has found that antibody levels (both maternal and those transferred to the newborn via the placenta) are highly associated with in vitro bactericidal activity, providing preliminary evidence of vaccine-mediated protection.
Figure 3. Protection of S. agalactiae vaccines in clinical development
(Source: Pena JMS, et al. 2024)
Nonetheless, the implementation of vaccines still has important open questions. To begin with, the scientific community is still debating what is the minimal antibody "protective threshold" that can confer sufficient immunity from infection in newborns, while also determining the best vaccination strategy (e.g. one dose per pregnancy is enough, or booster are required). The fact that, in some studies, a strong anamnestic antibody response has been observed upon re-administration of the vaccine even years after the first vaccination would indicate that a booster vaccination during each pregnancy could be a viable strategy.
Regarding progress in vaccine development, new-generation multivalent conjugate vaccines and protein-based vaccines have shown encouraging results. They not only induce durable antibodies in pregnant women and are efficiently transferred to the fetus but have also been demonstrated in animal models to protect offspring from lethal challenge. One major advance was also a technological innovation using new types of vaccine carriers, Qb virus-like particles (VLPs). Research showed that a vaccine using the Qb VLP carrier in a single dose caused a much stronger immune effect than two doses of a conventional carrier vaccine (for example, one using CRM197) and that this immune response lasted longer. This paves the way for new, more effective, and convenient single-dose vaccines.
References
| Target | Cat. No. | Product Name | Expression System | Tag/Conjugate | Application | |
| S. agalactiae | DAG-WT3651 | Inactivated Group B Streptococcus (GBS) Culture Fluid | N/A | N/A | Control | Inquiry |
| DAG-WT3652 | Inactivated Group B Streptococcus (GBS-Ia) Culture Fluid | N/A | N/A | Control | Inquiry | |
| DAG-WT3653 | Inactivated Group B Streptococcus (GBS-Ib) Culture Fluid | N/A | N/A | Control | Inquiry | |
| DAG-WT3654 | Inactivated Group B Streptococcus (GBS-III) Culture Fluid | N/A | N/A | Control | Inquiry | |
| S. agalactiae Hyaluronan Lyase protein | DAG2614 | Recombinant Streptococcus agalactiae Hyaluronan Lyase Protein (a.a. 259-1072) [His] | E. coli | His | N/A | Inquiry |
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