Distributions of candidate vaccine Targets, virulence Factors, and resistance features of invasive group B Streptococcus using Whole-Genome Sequencing: A Multicenter, population-based surveillance study.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. METHODS: We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. RESULTS: Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively." CONCLUSIONS: The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.

Sialic Acid-Siglec-E Interactions Regulate the Response of Neonatal Macrophages to Group B Streptococcus.

The mammalian Siglec receptor sialoadhesin (Siglec1, CD169) confers innate immunity against the encapsulated pathogen group B Streptococcus (GBS). Newborn lung macrophages have lower expression levels of sialoadhesin at birth compared with the postnatal period, increasing their susceptibility to GBS infection. In this study, we investigate the mechanisms regulating sialoadhesin expression in the newborn mouse lung. In both neonatal and adult mice, GBS lung infection reduced Siglec1 expression, potentially delaying acquisition of immunity in neonates. Suppression of Siglec1 expression required interactions between sialic acid on the GBS capsule and the inhibitory host receptor Siglec-E. The Siglec1 gene contains multiple STAT binding motifs, which could regulate expression of sialoadhesin downstream of innate immune signals. Although GBS infection reduced STAT1 expression in the lungs of wild-type newborn mice, we observed increased numbers of STAT1+ cells in Siglece-/- lungs. To test if innate immune activation could increase sialoadhesin at birth, we first demonstrated that treatment of neonatal lung macrophages ex vivo with inflammatory activators increased sialoadhesin expression. However, overcoming the low sialoadhesin expression at birth using in vivo prenatal exposures or treatments with inflammatory stimuli were not successful. The suppression of sialoadhesin expression by GBS-Siglec-E engagement may therefore contribute to disease pathogenesis in newborns and represent a challenging but potentially appealing therapeutic opportunity to augment immunity at birth.

Streptococcus agalactiae glycolipids promote virulence by thwarting immune cell clearance.

Streptococcus agalactiae [group B Streptococcus (GBS)] is a leading cause of neonatal meningitis, with late-onset disease (LOD) occurring after gastrointestinal tract colonization in infants. Bacterial membrane lipids are essential for host-pathogen interactions, and the functions of glycolipids are yet to be fully elucidated. GBS synthesizes three major glycolipids: glucosyl-diacylglycerol (Glc-DAG), diglucosyl-DAG (Glc2-DAG), and lysyl-Glc-DAG (Lys-Glc-DAG). Here, we identify the enzyme, IagB, as responsible for biosynthesis of Glc-DAG, the precursor for the two other glycolipids in GBS. To examine the collective role of glycolipids to GBS virulence, we adapted a murine model of neonatal meningitis to simulate LOD. The GBS∆iagB mutant traversed the gut-epithelial barrier comparable to wild type but was severely attenuated in bloodstream survival, resulting in decreased bacterial loads in the brain. The GBS∆iagB mutant was more susceptible to neutrophil killing and membrane targeting by host antimicrobial peptides. This work reveals an unexplored function of GBS glycolipids with their ability to protect the bacterial cell from host antimicrobial killing.

Protease SfpB plays an important role in cell membrane stability and immune system evasion in Streptococcus agalactiae.

Bacteria possess the ability to develop diverse and ingenious strategies to outwit the host immune system, and proteases are one of the many weapons employed by bacteria. This study sought to identify S. agalactiae additional serine protease and determine its role in virulence. The S. agalactiae THN0901 genome features one S8 family serine peptidase B (SfpB), acting as a secreted and externally exposed entity. A S8 family serine peptidase mutant strain (ΔsfpB) and complement strain (CΔsfpB) were generated through homologous recombination. Compared to the wild-type strain THN0901, the absorption of EtBr dyes was significantly reduced (P < 0.01) in ΔsfpB, implying an altered cell membrane permeability. In addition, the ΔsfpB strain had a significantly lower survival rate in macrophages (P < 0.01) and a 61.85 % lower adhesion ability to the EPC cells (P < 0.01) compared to THN0901. In the in vivo colonization experiment using tilapia as a model, 210 fish were selected and injected with different bacterial strains at a concentration of 3 × 106 CFU/tail. At 6, 12, 24, 48, 72 and 96 h post-injection, three fish were randomly selected from each group and their brain, liver, spleen, and kidney tissues were isolated. Subsequently, it was demonstrated that the ΔsfpB strain exhibited a markedly diminished capacity for colonization in tilapia. Additionally, the cumulative mortality of ΔsfpB in fish after intraperitoneal injection was reduced by 19.92-23.85 %. In conclusion, the findings in this study have demonstrated that the SfpB plays a significant role in S. agalactiae cell membrane stability and immune evasion. The immune evasion is fundamental for the development and transmission of invasive diseases, the serine protease SfpB may be a promising candidate for the development of antimicrobial agents to reduce the transmission of S. agalactiae.

Comparative analysis of Streptococcus agalactiae serotypes Ia and II isolates from China and Pakistan in a murine model: A focus on pathogenesis and immune response.

Bovine mastitis, caused by Streptococcus agalactiae (Group B Streptococcus; GBS), poses significant economic challenges to the global dairy industry. Mouse models serves as valuable tools for assessing GBS-induced infections as an alternative to large animals. This study aimed to investigate the LD50 dose, organ bacterial load, and quantification of peritoneal leukocyte populations for GBS serotypes Ia and II isolates from China and Pakistan. Additionally, we measured indicators such as lactoferrin, albumin, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-2) and anti-inflammatory cytokines (IL-10 and TGF-ß) in serum and tissue samples were evaluated using ELISA and qPCR, respectively. BALB/c mice (4 mice per group) received individual intraperitoneal injections of 100 µl containing specific bacterial inoculum concentrations (ranging from 105 to 109 CFU per mouse) of Chinese and Pakistani GBS isolates (serotypes Ia and II). Control groups received 100 µL of sterile PBS. Results revealed that the LD50 bacterial dose causing 50 % mortality in mice was 107 CFU. The highest bacterial load in all experimental groups was quantified in the peritoneum, followed by blood, mammary gland, liver, spleen, lungs, and brain. The most significant bacterial dissemination was observed in mice inoculated with Pakistani serotype Ia at 24 h, with a subsequent notable decline in bacterial counts at day 3. Notably, infection with Pakistani serotype Ia showed a trend of increased total leukocyte counts, significantly higher than Pakistani serotype II, Chinese Serotype Ia, and Chinese serotype II. A substantial influx of neutrophils and lymphocytes was observed in response to all tested serotypes, with Pakistani serotype Ia inducing a significantly higher influx compared to other groups (Pakistani serotype II, Chinese serotype Ia, and Chinese serotype II). Furthermore, TNF-α, IL-1ß, IL-2, and IL-6 expressions were significantly increased in mice one day after infection with the Pakistani serotype Ia. Compared to mice infected with the Pakistani serotype II, Chinese Serotype Ia, and Chinese serotype II, those infected with the Pakistani serotype Ia isolate exhibited the highest production of IL-10 and TGF-ß, along with significantly increased concentrations of lactoferrin, albumin, and MPO. These findings suggest that the persistence and severity of infection caused by the Pakistani serotype Ia may be linked to its ability to spread to deeper tissues. This study enhances our understanding of the clinical characteristics of bovine mastitis caused by S. agalactiae in China and Pakistan.

Antibody kinetics between birth and three months of life in healthy infants with natural exposure to Group B streptococcus: A UK cohort study.

INTRODUCTION: Capsular polysaccharide (CPS) serotype-specific Immunoglobulin G (IgG) in cord blood has been proposed as a correlate of protection against invasive Group B Streptococcus (iGBS) disease. Although protective levels are required in infants throughout the window of vulnerability up to 3 months of age, little is known regarding the kinetics of GBS-specific IgG over this period. METHODS: We enrolled 33 healthy infants born to mothers colonized with GBS. We collected cord blood and infant blood samples either at one (21-35 days), two (49-63 days), or three months of age (77-91 days). We measured GBS serotype-specific CPS IgG concentrations and calculated the decay rate using a mixed-effects model. We further explored whether the antibody kinetics were affected by common maternal and infant factors and estimated the correlation between IgG concentration at birth and one, two, and three months of age. RESULTS: The half-life estimate of IgG concentration for homologous and non-homologous GBS serotypes in paired samples with detectable IgG levels at both time points was 27.4 (95 % CI: 23.5-32.9) days. The decay rate did not vary by maternal age (p = 0.7), ethnicity (p = 0.1), gravida (p = 0.1), gestation (p = 0.7), and infant sex (p = 0.1). Predicted IgG titres above the assay lower limit of quantification on day 30 strongly correlated with titres at birth (Spearman correlation coefficient 0.71 [95 % CI: 0.60-0.80]). CONCLUSION: Our results provide a basis for future investigations into the use of antibody kinetics in defining a serocorrelate of protection against late-onset iGBS disease.

Induction of trained immunity using ß-glucan and its protective responses in Nile tilapia, Oreochromis niloticus.

Emerging and re-emerging diseases in fish cause drastic economic losses in the aquaculture sector. To combat the impact of disease outbreaks and prevent the emergence of infections in culture systems, understanding the advanced strategies for protecting fish against infections is inevitable in fish health research. Therefore, the present study aimed to evaluate the induction of trained immunity and its protective efficacy against Streptococcus agalactiae in tilapia. For this, Nile tilapia and the Tilapia head kidney macrophage primary culture were primed using ß-glucan @200 µg/10 g body weight and 10 µg/mL respectively. Expression profiles of the markers of trained immunity and production of metabolites were monitored at different time points, post-priming and training, which depicted enhanced responsiveness. Higher lactate and lactate dehydrogenase (LDH) production in vitro suggests heightened glycolysis induced by priming of the cells using ß-glucan. A survival rate of 60% was observed in ß-glucan trained fish post challenge with virulent S. agalactiae at an LD50 of 2.6 × 107 cfu/ml, providing valuable insights into promising strategies of trained immunity for combating infections in fish.

Recombinant lactococcal-based oral vaccine for protection against Streptococcus agalactiae infections in tilapia (Oreochromis niloticus).

Streptococcosis outbreaks caused by Streptococcus agalactiae infection in tilapia aquaculture have been consistently reported and associated with high mortality and morbidity leading to significant economic losses. Existing vaccine candidates against Streptococcus spp. are designed for intraperitoneal injections that are not practical and labor-intensive which have prompted farmers to protect aquatic animals with antibiotics, thus encouraging the emergence of multidrug resistant bacteria. In this study, a live recombinant L. lactis vaccine expressing a 1403 bp surface immunogenic protein (SIP) and a 1100 bp truncated SIP (tSIP) gene was developed and evaluated against S. agalactiae infection in tilapia. Both SIP and tSIP sequences were cloned and transformed into L. lactis. The recombinant L.lactis vaccine was orally administered to juvenile tilapia for a month. Detection of SIP-specific serum IgM in vaccinated groups compared to control groups indicated that recombinant proteins expressed from L. lactis could elicit immunogenic reactions in tilapia. Fish immunized with the tSIP vaccine also showed the highest level of protection compared to other test groups, and the mortality rate was significantly reduced compared to both control groups. The relative percentage of survival (RPS) against S. agalactiae for both SIP and tSIP-vaccinated groups was 50 % and 89 %, respectively, at 14 days post-challenge. Significant up-regulation of IgM, IL-1ß, IL-10, TNF-α and IFN-γ were observed at day 34 between the vaccinated and control groups. These results indicated that the recombinant lactococcal tSIP vaccine can elicit both cell-mediated and humoral responses and is recommended as a potential oral vaccine against S. agalactiae infection. Future work will include further in vivo challenge assessments of this vaccine candidate fused with adjuvants to boost immunogenicity levels in tilapia.

Evaluation of the efficacy of MONTANIDE™ GR01, a new adjuvant for feed-based vaccines, on the immune response and protection against Streptococcus agalactiae in oral vaccinated Nile tilapia (Oreochromis niloticus) under laboratory and on-farm conditions.

Streptococcosis, an emerging infectious disease caused by Streptococcus agalactiae, has had adverse effects on farmed tilapia. Several vaccines have been developed to prevent this disease and induce a specific immune response against S. agalactiae infection. In this study the use of MONTANIDE™ GR01, a new adjuvant for oral vaccination, was optimized for use in tilapia under laboratory and field studies. In the laboratory trial the immune response and protective efficacy of two doses of MONTANIDE™ GR01, 20 % (w/w) and 2 % (w/w), included into the feed-based adjuvanted vaccines were assessed comparatively. Following immunization, the innate immune parameters studied in serum, including lysozyme, myeloperoxidase, catalase and glutathione peroxidase activity, were all increased significantly. Furthermore, specific IgM antibodies against S. agalactiae were induced significantly in serum post-vaccination, with higher levels observed in both groups that received the feed-based adjuvanted vaccine. Under both injection and immersion challenge conditions, the relative percent survival for the feed-based adjuvanted vaccine groups ranged from 78 % to 84 %. Following use of the low dose concentration of MONTANIDE™ GR01 for oral vaccination of tilapia in cage culture systems, several innate immune parameters were effectively enhanced in the immunized fish. Similarly, the levels of specific IgM antibodies in the serum of feed-based vaccinated fish were significantly enhanced, reaching their highest levels 2-5 months post-vaccination. Cytokines associated with innate and adaptive immunity were also examined, and the expression levels of several genes showed significant up-regulation. This indicates that both cellular and humoral immune responses were induced by the feed-based adjuvanted vaccine. The economic impact of a feed-based adjuvanted vaccine was examined following vaccination, considering the growth performance and feed utilization of the fish. It was found that the Economic Performance Index and Economic Conversion Ratio were unaffected by vaccination, further demonstrating that there are no negative impacts associated with administering a feed-based vaccine to fish. In conclusion, the data from this study indicate that MONTANIDE™ GR01 is a highly valuable adjuvant for oral vaccination, as demonstrated by its ability to induce a strong immune response and effectively prevent streptococcal disease in Nile tilapia.

Expression of immuno-transcriptome response in red hybrid tilapia (Oreochromis sp.) hindgut following vaccination with feed-based bivalent vaccine.

Streptococcosis and aeromoniasis are the main obstacles to sustainable tilapia production. Vaccination offered an effective method to control microbial infections. Previously, a feed-based bivalent vaccine (FBBV) containing killed whole organisms of Streptococcus agalactiae and Aeromonas hydrophila mixed with 10% palm oil was successfully developed, which provided good protection against streptococcosis and aeromoniasis in Oreochromis sp. However, the mechanisms of immunities in vaccinated fish still need clarification. Here, the hindgut transcriptome of vaccinated and control fish was determined, as the gut displays higher affinity towards antigen uptake and nutrient absorption. The efficacy of FBBV to improve fish immunity was evaluated according to the expression of immune-related genes in the vaccinated fish hindgut throughout the 8-week experimental period using RT-qPCR. The vaccinated fish hindgut at week 6 was further subjected to transcriptomic analysis due to the high expression of immune-related genes and contained killed whole organisms. Results demonstrated the expression of immune-related genes was in correlation with the presence of killed whole organisms in the vaccinated fish hindgut. Transcriptomic analysis has allowed the prediction of robust immune-related pathways, including innate and adaptive immunological responses in vaccinated fish hindgut than control fish. Pathways related to the regulation of lipid metabolism and modulation of the immune system were also significantly enriched (p ≤ .05). Overall, results offer a fundamental study on understanding the immunological response in Oreochromis sp. following vaccination with the FBBV pellet and support further application to prevent bacterial diseases in aquaculture.

Bacteria hijack a meningeal neuroimmune axis to facilitate brain invasion.

The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache1,2. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system, affecting more than 2.5 million people a year3-5. How pain and neuroimmune interactions impact meningeal antibacterial host defences are unclear. Here we show that Nav1.8+ nociceptors signal to immune cells in the meninges through the neuropeptide calcitonin gene-related peptide (CGRP) during infection. This neuroimmune axis inhibits host defences and exacerbates bacterial meningitis. Nociceptor neuron ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. S. pneumoniae activated nociceptors through its pore-forming toxin pneumolysin to release CGRP from nerve terminals. CGRP acted through receptor activity modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transcriptional responses, suppressing macrophage chemokine expression, neutrophil recruitment and dural antimicrobial defences. Macrophage-specific RAMP1 deficiency or pharmacological blockade of RAMP1 enhanced immune responses and bacterial clearance in the meninges and brain. Therefore, bacteria hijack CGRP-RAMP1 signalling in meningeal macrophages to facilitate brain invasion. Targeting this neuroimmune axis in the meninges can enhance host defences and potentially produce treatments for bacterial meningitis.

Toward the development of a protein-based group B Streptococcus vaccine.

Clinical trials of protein-based vaccines to prevent Group B streptococcal infections are underway. In this issue of Cell Reports Medicine, Pawlowski et al.1 provide an extensive characterization of the immune response generated by the recently tested GBS-NN vaccine.

Group B Streptococcus Surface Protein ß: Structural Characterization of a Complement Factor H-Binding Motif and Its Contribution to Immune Evasion.

The ß protein from group B Streptococcus (GBS) is a ∼132-kDa, cell-surface exposed molecule that binds to multiple host-derived ligands, including complement factor H (FH). Many details regarding this interaction and its significance to immune evasion by GBS remain unclear. In this study, we identified a three-helix bundle domain within the C-terminal half of the B75KN region of ß as the major FH-binding determinant and determined its crystal structure at 2.5 Å resolution. Analysis of this structure suggested a role in FH binding for a loop region connecting helices α1 and α2, which we confirmed by mutagenesis and direct binding studies. Using a combination of protein cross-linking and mass spectrometry, we observed that B75KN bound to complement control protein (CCP)3 and CCP4 domains of FH. Although this binding site lies within a complement regulatory region of FH, we determined that FH bound by ß retained its decay acceleration and cofactor activities. Heterologous expression of ß by Lactococcus lactis resulted in recruitment of FH to the bacterial surface and a significant reduction of C3b deposition following exposure to human serum. Surprisingly, we found that FH binding by ß was not required for bacterial resistance to phagocytosis by neutrophils or killing of bacteria by whole human blood. However, loss of the B75KN region significantly diminished bacterial survival in both assays. Although our results show that FH recruited to the bacterial surface through a high-affinity interaction maintains key complement-regulatory functions, they raise questions about the importance of FH binding to immune evasion by GBS as a whole.

Assessing the added value of group B Streptococcus maternal immunisation in preventing maternal infection and fetal harm: population surveillance study.

OBJECTIVE: To assess the incidence of maternal group B Streptococcus (GBS) infection in England. DESIGN: Population surveillance augmented through data linkage. SETTING: England. POPULATION: All pregnant women accessing the National Health Service (NHS) in England. METHODS: Invasive GBS (iGBS) infections during pregnancy or within 6 weeks of childbirth were identified by linking Public Health England (PHE) national microbiology surveillance data for 2014 to NHS hospital admission records. Capsular serotypes of GBS were determined by reference laboratory typing of clinical isolates from women aged 15-44 years. Post-caesarean section surgical site infection (SSI) caused by GBS was identified in 21 hospitals participating in PHE SSI surveillance (2009-2015). MAIN OUTCOME MEASURES: iGBS rate per 1000 maternities; risk of GBS SSI per 1000 caesarean sections. RESULTS: Of 1601 patients diagnosed with iGBS infections in England in 2014, 185 (12%) were identified as maternal infections, a rate of 0.29 (95% CI 0.25-0.33) per 1000 maternities and representing 83% of all iGBS cases in women aged 18-44 years. Seven (3.8%) were associated with miscarriage. Fetal outcome identified excess rates of stillbirth (3.4 versus 0.5%) and extreme prematurity (<28 weeks of gestation, 3.7 versus 0.5%) compared with national averages (P < 0.001). Caesarean section surveillance in 27 860 women (21 hospitals) identified 47 cases of GBS SSI, with an estimated 4.24 (3.51-5.07) per 1000 caesarean sections, a median time-to-onset of 10 days (IQR 7-13 days) and ten infections that required readmission. Capsular serotype analysis identified a diverse array of strains with serotype III as the most common (43%). CONCLUSIONS: Our assessment of maternal GBS infection in England indicates the potential additional benefit of GBS vaccination in preventing adverse maternal and fetal outcomes.

Testing Novel Inactivation Methods and Adjuvants for Vaccines Against Streptococcus agalactiae in Nile Tilapia Oreochromis niloticus.

Inactivation by hydrogen peroxide and pH manipulation are two novel methods used recently in experimental vaccines against Streptococcus agalactiae in Nile tilapia. Here we describe in detail inactivation using novel methods as well as the classical method of inactivation. These vaccines showed similar moderate efficacy when compared to the conventional formaldehyde vaccine. In addition, we describe the inclusion of adjuvants in a hydrogen peroxide vaccine.

Fpr2/CXCL1/2 Controls Rapid Neutrophil Infiltration to Inhibit Streptococcus agalactiae Infection.

Streptococcus agalactiae, also known as group B streptococcus (GBS), can cause pneumonia, meningitis, and bacteremia, making it a pathogen that can increase the risk of death in newborns and immunodeficient individuals. Neutrophils are the first barrier to a host's innate immune defense against these infections. Fpr2(Formyl peptide receptor 2) is an important chemotactic receptor of neutrophils, though its activation would cause pro- and anti-inflammatory effects. In this study, we found that mice without Fpr2 receptor were highly susceptible to GBS infections. These mice demonstrated decreased chemotaxis to neutrophils, decreased bactericidal ability of neutrophils, and high mortality. RNA-seq and Luminex assay indicated that Fpr2 activates key signal molecules downstream and produces chemokines CXCL1/2 to chemotaxis neutrophils. Like Fpr2-/-, CXCL1/2 or neutrophil depletion impairs host's ability to defend against GBS infection. Altogether, these data indicate that Fpr2 contributes to a host's ability to control GBS infection and that a lack of Fpr2 was associated with selective impairment during the production of chemokines CXCL1 and CXCL2 as well as neutrophil recruitment. Here, We clarified that Fpr2, as a chemotactic receptor, could not only directly chemotactic neutrophils, but also regulate the production of chemokines to control infection by chemotactic neutrophils.

Maternal vaccination with a type-III glycoconjugate protects mouse neonates against Group B Streptococcus intranasal infection.

Group B Streptococcus (GBS) is generally an asymptomatic colonizer of human mucosa but it occasionally infects pregnant women and neonates through vertical transmission, causing disease during the first weeks of life with frequent and severe complications. Preclinical studies have shown that maternal vaccination with polysaccharide-based vaccines protects mothers and offspring from GBS mucosal colonization and consecutive infection. In these models, bacteria were inoculated in mouse either intravaginally in the last trimester of pregnancy or systemically in pups. Here, we investigated whether maternal vaccination with glycoconjugate vaccines may also prevent GBS-mediated colonization and disease in neonates using an infection route that more closely mimics inhalation or ingestion of bacteria during human delivery. To address this point, mice aged less than two days were intranasally challenged with epidemiologically relevant GBS strains. Bacteria were found to colonize nose and intestine, reaching in some cases lungs and blood during the first days of life. Bacteria were also found in vagina of a fraction of colonized female mice within the first month of life. GBS-specific IgG induced by maternal vaccination with a glycoconjugate vaccine formulation were found in blood and mucosal tissues of newborns. Finally, when intranasally challenged with GBS serotype III strains, pups delivered by vaccinated mothers were partially protected against mucosal colonization and deeper infection.

Group B streptococcal infections in infants in Iceland: clinical and microbiological factors.

Introduction. Group B streptococcus (GBS) is a leading cause of invasive neonatal infections. These have been divided into early-onset disease (EOD; <7 days) and late-onset disease (LOD; 7-89 days), with different GBS clonal complexes (CCs) associated with different disease presentations.Hypothesis. Different GBS CCs are associated with timing of infection (EOD or LOD) and clinical presentation (sepsis, meningitis or pneumonia).Aim. To study infant GBS infections in Iceland from 1975 to 2019. Are specific GBS CCs related to disease presentation? Is CC17 overrepresented in infant GBS infections in Iceland?Methodology. All culture-confirmed invasive GBS infections in infants (<90 days) in Iceland from 1975 to 2019 were included. Clinical information was gathered from medical records.Results. A total of 127 invasive GBS infections in infants were diagnosed, but 105 infants were included in the study. Of these, 56 had EOD and 49 had LOD. The incidence of GBS infections declined from 2000 onwards but increased again at the end of the study period. Furthermore, there was a significant increase in LOD over the study period (P=0.0001). The most common presenting symptoms were respiratory difficulties and fever and the most common presentation was sepsis alone. Approximately one-third of the cases were caused by GBS CC17 of serotype III with surface protein RIB and pili PI-1+PI-2b or PI-2b. CC17 was significantly associated with LOD (P<0.001).Conclusion. CC17 is a major cause of GBS infection in infants in Iceland. This clone is associated with LOD, which has been increasing in incidence. Because intrapartum antibiotic prophylaxis only prevents EOD, it is important to continue the development of a GBS vaccine in order to prevent LOD infections.

Immunogenicity in Oreochromis niloticus vaccinated with sonicated antigens against streptococcosis.

Streptococcosis causes great economic losses in intensive culture of tilapia. Vaccination is the most effective and safest way to tackle infectious diseases. Thus, this study sought the more effective and safer antigenic fraction after sonication of Streptococcus agalactiae to elaborate a vaccine against streptococcosis in Nile tilapia. For this, twenty-one days after vaccination with different fractions (soluble and insoluble) of S. agalactiae, the fish were challenged with the homologous strain (LD50). Then, samples were taken at zero, 14, 28, 60 and 90 days post-vaccination (DPV, n = 7). Blood and organs (cranial kidney, spleen and liver) were collected from vaccinated and unvaccinated fish. Finally, insoluble fraction vaccine presented the best effect, resulting in a 100% relative percent of survival (RPS) and without clinical manifestations. In view of the results, it was to evaluate the role of the insoluble fraction of the antigen in the protective immunity against streptococcosis. The results indicate that the spleen might be the main organ in the vaccine response in Nile tilapia due to the great morphological and immunological differences in vaccinated fish, evidenced by the greater of melanomacrophage centers (MMC) and IgM + lymphocytes in relation to the non-vaccinated fish. At 60 DPV, it was observed the peak of the protective immunity related to the maximum concentration of proteins, circulating leukocytes, antibody titers in the serum and tissue changes with greater expression of IgM + and MMC number in the spleen and kidney of Oreochromis niloticus. Vaccination with insoluble fraction of S. agalactiae was safe and provided effective protection against streptococcosis with maximum protective response at 60 DPV.