RESUMEN
BACKGROUND: Group A Streptococcus (Strep A) causes both uncomplicated and severe invasive infections, as well as the post-infection complications acute rheumatic fever and rheumatic heart disease. Despite the high global burden of disease resulting from Strep A infections, there is not a licensed vaccine. A 30-valent M protein-based vaccine has previously been shown to be immunogenic in animal models and in a Phase I clinical trial (NCT02564237). Here, we assessed the immunogenicity of a 30-valent messenger (m)RNA vaccine designed to express the same M peptide targets as the 30-valent protein vaccine and compared it with the protein vaccine. METHODS: Female New Zealand white rabbits were immunized with one of four vaccine formulations (3 doses of each formulation at days 1, 28, and 56): soluble mRNA (100 µg/animal), C-terminal transmembrane mRNA (100 µg/animal), protein vaccine (400 µg/animal), or a non-translatable RNA control (100 µg/animal). Serum was collected one day prior to the first dose and on days 42 and 70. Rabbit serum samples were assayed for antibody levels against synthetic M peptides by ELISA. HL-60 opsonophagocytic killing (OPK) assays were performed to assess functional antibody levels. RESULTS: Serum IgG levels were similar for the mRNA and protein vaccines. The CtTM version of the mRNA vaccine elicited slightly higher antibody levels than the mRNA designed to express soluble proteins. OPK activity was similar for the mRNA and protein vaccines, regardless of M type. CONCLUSIONS: The total antibody responses and functional antibody levels elicited by the 30-valent mRNA Strep A vaccines were similar to those observed following immunization with the analogous protein vaccine. The mRNA vaccine platform provides potential advantages to protein-based vaccines including inherent adjuvant activity, increased production efficiency, lower cost, and the potential to rapidly change epitopes/peptides, all of which are important considerations related to multivalent Strep A vaccine development.
Asunto(s)
Anticuerpos Antibacterianos , Antígenos Bacterianos , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus pyogenes , Animales , Conejos , Femenino , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Vacunas Estreptocócicas/genética , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética , Streptococcus pyogenes/inmunología , Streptococcus pyogenes/genética , Inmunogenicidad Vacunal , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Portadoras/inmunología , Proteínas Portadoras/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , ARN Mensajero/genética , ARN Mensajero/inmunologíaRESUMEN
INTRODUCTION: Current protocols aim to prevent some infant GBS infection through screening and peripartum antibiotics, however such strategies cannot be widely implemented in resource-limited settings. On the other hand, maternal vaccines in development against Group B Streptococcus (GBS) can provide a feasible universal approach. The success of any vaccine will depend on uptake in the population. Rates of maternal GBS colonization in the Dominican Republic (DR) and Caribbean region are among the highest in the world, but little is known about attitudes towards maternal vaccines in this region. METHODS: A cross-sectional, multicenter, mixed-methodology survey evaluated facilitators and barriers to maternal immunization and acceptability of a hypothetical Group B Streptococcus vaccine among pregnant women in three hospitals in the DR. RESULTS: Six-hundred and fifty women completed the survey of whom 85 % had never heard of GBS. Following receipt of information about GBS and a vaccine, 94 % of women stated that they would be likely or very likely to receive a vaccine. Being 18 years or younger was associated with a lower likelihood of GBS vaccine receipt (AOR 0.32, 95 % CI 0.14-0.69). Being born in the DR was associated with a higher likelihood of GBS vaccine receipt (AOR 2.73, 95 % CI 1.25-5.97). Among women who were unlikely to receive the vaccine, uncertainty about potential harm from a novel vaccine was the prominent theme elicited from free text responses. CONCLUSION: There was a high level of acceptance of a future GBS vaccine among this sample of pregnant women in the DR. However, knowledge of vaccines and vaccine-preventable diseases was low, and most women had concerns about the safety of new vaccines. Interventions that strengthen existing maternal immunisation infrastructures, including increasing education of pregnant women about vaccines, will aid the successful implementation of a future GBS vaccine.
Asunto(s)
Complicaciones Infecciosas del Embarazo , Mujeres Embarazadas , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus agalactiae , Humanos , Femenino , Embarazo , República Dominicana , Adulto , Estudios Transversales , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Streptococcus agalactiae/inmunología , Adulto Joven , Mujeres Embarazadas/psicología , Complicaciones Infecciosas del Embarazo/prevención & control , Adolescente , Encuestas y Cuestionarios , Vacunación/psicología , Vacunación/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
Group B Streptococcus (GBS) disease in neonates occurs in two forms: early-onset disease (EOD), (day 0-6), and late-onset disease (LOD), (day 7-90). This review investigates that risk-based intrapartum screening and antibiotics have reduced the incidence of EOD, but not LOD, in Denmark. No clinical or laboratory tests can rule out GBS disease at symptom onset. Thus, a high proportion of uninfected infants receive antibiotics, although this varies widely, and may be reduced by strategies of antibiotic stewardship. A future GBS vaccine for pregnant women may potentially reduce disease burden and antibiotic exposure.
Asunto(s)
Antibacterianos , Infecciones Estreptocócicas , Streptococcus agalactiae , Humanos , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/tratamiento farmacológico , Recién Nacido , Streptococcus agalactiae/aislamiento & purificación , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Femenino , Embarazo , Dinamarca/epidemiología , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Lactante , Vacunas Estreptocócicas/administración & dosificación , Transmisión Vertical de Enfermedad Infecciosa/prevención & controlRESUMEN
Subunit vaccines require an immunostimulant (adjuvant) and/or delivery system to induce immunity. However, currently, available adjuvants are either too dangerous in terms of side effects for human use (experimental adjuvants) or have limited efficacy and applicability. In this study, we examined the capacity of mannose-lipopeptide ligands to enhance the immunogenicity of a vaccine consisting of polyleucine(L15)-antigen conjugates anchored to liposomes. The clinically tested Group A Streptococcus (GAS) B-cell epitope, J8, combined with universal T helper PADRE (P) was used as the antigen. Six distinct mannose ligands were incorporated into neutral liposomes carrying L15PJ8. While induced antibody titers were relatively low, the ligand carrying mannose, glycine/lysine spacer, and two palmitic acids as liposomal membrane anchoring moieties (ligand 3), induced significantly higher IgG titers than non-mannosylated liposomes. The IgG titers were significantly enhanced when positively charged liposomes were employed. Importantly, the produced antibodies were able to kill GAS bacteria. Unexpectedly, the physical mixture of only ligand 3 and PJ8 produced self-assembled nanorods that induced antibody titers as high as those elicited by the lead liposomal formulation and antigen adjuvanted with the potent, but toxic, complete Freund's adjuvant (CFA). Antibodies produced upon immunization with PJ8 + 3 were even more opsonic than those induced by CFA + PJ8. Importantly, in contrast to CFA, ligand 3 did not induce observable adverse reactions or excessive inflammatory responses. Thus, we demonstrated that a mannose ligand, alone, can serve as an effective vaccine nanoadjuvant.
Asunto(s)
Adyuvantes Inmunológicos , Liposomas , Manosa , Liposomas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Manosa/inmunología , Animales , Ratones , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Femenino , Ligandos , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Streptococcus pyogenes/inmunología , Adyuvantes de Vacunas/administración & dosificación , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Ratones Endogámicos BALB CRESUMEN
Streptococcus suis is a bacterial pathogen that can cause significant economic losses in the swine industry due to high morbidity and mortality rates in infected animals. Vaccination with bacterins, which consist of inactivated bacteria and adjuvants to enhance the pig's immune response, is an effective approach to control S. suis infections in piglets. Here we provide a description of S. suis bacterins and the methods for vaccine preparation. Moreover, this chapter also describes the addition of recombinant Sao (rSao-L) protein to the S. suis bacterin, aiming to enhance the efficacy of the bacterins against S. suis in piglets. Furthermore, the methods for evaluating the immune response elicited by the bacterins are also covered in this chapter.
Asunto(s)
Streptococcus suis , Animales , Porcinos , Streptococcus suis/inmunología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/veterinaria , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/inmunología , Vacunación/métodos , Vacunas Bacterianas/inmunología , Adyuvantes Inmunológicos/farmacología , Anticuerpos Antibacterianos/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificaciónRESUMEN
Streptococcus suis is one of the major pathogens of pigs circulating worldwide, and the development of vaccines will help to effectively control streptococcosis in swine. In this study, we evaluated the potential of three membrane associated proteins, histidine kinase (HK), glycosyltransferase family 2 (Gtf-2) and phosphate binding protein (PsbP) of S. suis as subunit vaccines. Bioinformatics analysis shows that protein ABC is highly conserved in S. suis. To verify the protective effects of these proteins in animal models, recombinant protein HK, Gtf-2 and PsbP were used to immunize BALB/c mice separately. The results showed that these proteins immunization in mice can effectively induce strong humoral immune responses, protect mice from cytokine storms caused by S. suis infection, and have a significant protective effect against lethal doses of S. suis infection. Furthermore, antibodies with opsonic activity exist in the recombinant proteins antiserum to assist phagocytic cells in killing S. suis. Overall, these results indicated that these recombinant proteins all elicit good immune protective effect against S. suis infection and can be represent promising candidate antigens for subunit vaccines against S. suis.
Asunto(s)
Anticuerpos Antibacterianos , Proteínas Bacterianas , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Proteínas Recombinantes , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus suis , Vacunas de Subunidad , Streptococcus suis/inmunología , Streptococcus suis/genética , Animales , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Ratones , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/genética , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Vacunas Estreptocócicas/genética , Serogrupo , Citocinas/metabolismo , Femenino , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/genética , Inmunidad Humoral , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/microbiología , Porcinos , Biología ComputacionalRESUMEN
Strangles is a highly contagious disease of the equine upper respiratory tract caused by Streptococcus equi subspecies. Streptococcus equi subsp. equi (S. equi) and Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) was isolated, as local, hot, and field strains, from horses clinically suffering from respiratory distress. The isolated Streptococci were identified using bacteriological and molecular techniques. Four formulations of inactivated S. equi vaccines were developed and evaluated. The first formulation was prepared using the S. equi isolates, adjuvanted with MONTANIDE GEL adjuvant, while the second formulation was adjuvanted with MONTANIDE ISA-70 adjuvant. The other 2 formulations were inactivated combined vaccines prepared from both S. equi and S. zooepidemicus isolates. The 3rd formulation was the combined isolates adjuvanted with MONTANIDE GEL while the 4th formulation was the combined isolates adjuvanted with MONTANIDE ISA-70. The developed vaccines' physical properties, purity, sterility, safety, and potency were ensured. The immunizing efficacy was determined in isogenic BALB/c mice and white New Zealand rabbits using the passive hemagglutination test. Also, the antibodies' titer of the combined S. equi and S. zooepidemicus vaccine adjuvanted with MONTANIDE ISA-70 in foals was tracked using an indirect enzyme-linked immunosorbent assay. The protective efficacy of the developed vaccines was determined using a challenge test in both laboratory and field animal models, where a 75% protection rate was achieved. The combined vaccine proved to be more efficacious than the monovalent vaccine. Also, the MONTANIDE ISA-70 adjuvant provided significant protective efficacy than the MONTANIDE GEL. The current work is introducing a very promising mitigative and strategic controlling solution for strangles.
Asunto(s)
Enfermedades de los Caballos , Ratones Endogámicos BALB C , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus equi , Streptococcus , Animales , Streptococcus equi/inmunología , Caballos , Conejos , Infecciones Estreptocócicas/veterinaria , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/inmunología , Ratones , Enfermedades de los Caballos/prevención & control , Enfermedades de los Caballos/microbiología , Enfermedades de los Caballos/inmunología , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Femenino , Anticuerpos Antibacterianos/sangre , Adyuvantes Inmunológicos/administración & dosificación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Dental caries is a prevalent oral disease that mainly results from Streptococcus mutans. Susceptibility to S. mutans decreased rapidly after weaning in a well-known rat model. However, owing to the lack of time to establish protective immunity ahead of challenge, the weaning rat model is suboptimal for assessing prophylactic vaccines against S. mutans infection. In this study, we found that, in adult rats, S. mutans cultured under air-restricted conditions showed dramatically increased colonization efficacy and accelerated development of dental caries compared with those cultured under air-unrestricted conditions. We propose that S. mutans cultured under air-restricted conditions can be used to develop an optimal caries model, especially for the evaluation of prophylactic efficacy against S. mutans. Therefore, we used the anti-caries vaccine, KFD2-rPAc, to reevaluate the protection against the challenge of S. mutans. In immunized rats, rPAc-specific protective antibodies were robustly elicited by KFD2-rPAc before the challenge. In addition to inhibiting the initial and long-term colonization of S. mutans in vivo, KFD2-rPAc immunization showed an 83% inhibitory efficacy against the development of caries, similar to that previously evaluated in a weaning rat model. These results demonstrate that culturing under air-restricted conditions can promote S. mutans infection in adult rats, thereby helping establish a rat infection model to evaluate the prophylactic efficacy of vaccines and anti-caries drugs.
Asunto(s)
Anticuerpos Antibacterianos , Caries Dental , Modelos Animales de Enfermedad , Streptococcus mutans , Animales , Caries Dental/prevención & control , Caries Dental/microbiología , Caries Dental/inmunología , Streptococcus mutans/inmunología , Ratas , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Femenino , Ratas Sprague-DawleyRESUMEN
Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no current commercial vaccines, the use of autogenous vaccines applied to gilts/sows to enhance transfer of passive immunity is an attractive alternative to protect weaned piglets. However, there is no universal standardization in the production of autogenous vaccines and the vaccine formulation may be highly different among licenced manufacturing laboratories. In the present study, an autogenous vaccine that included S. suis serotypes 2, 1/2, 5, 7 and 14 was prepared by a licensed laboratory and administrated to gilts using a three-dose program prior to farrowing. The antibody response in gilts as well as the passive transfer of antibodies to piglets was then evaluated. In divergence with previously published data with an autogenous vaccine produced by a different company, the increased response seen in gilts was sufficient to improve maternal antibody transfer to piglets up to 5 weeks of age. However, piglets would still remain susceptible to S. suis disease which often appears during the second part of the nursery period. Vaccination did not affect the shedding of S. suis (as well as that of the specific S. suis serotypes included in the vaccine) by either gilts or piglets. Although all antibiotic treatments were absent during the trial, the clinical protective effect of the vaccination program with the autogenous vaccine could not be evaluated, since limited S. suis cases were present during the trial, confirming the need for a complete evaluation of the clinical protection that must include laboratory confirmation of the aetiological agent involved in the presence of S. suis-associated clinical signs. Further studies to evaluate the usefulness of gilt/sow vaccination with autogenous vaccines to protect nursery piglets should be done.
Asunto(s)
Autovacunas , Infecciones Estreptocócicas , Streptococcus suis , Enfermedades de los Porcinos , Animales , Streptococcus suis/inmunología , Porcinos , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/inmunología , Infecciones Estreptocócicas/veterinaria , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Femenino , Inmunidad Materno-Adquirida , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Serogrupo , Vacunación/veterinariaRESUMEN
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.
Asunto(s)
Cíclidos , Enfermedades de los Peces , Infecciones Estreptocócicas , Streptococcus agalactiae , Animales , Streptococcus agalactiae/inmunología , Infecciones Estreptocócicas/veterinaria , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/inmunología , Cíclidos/inmunología , Administración Oral , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Lactococcus lactis/genética , Lactococcus lactis/inmunología , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/genéticaRESUMEN
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.
Asunto(s)
Adyuvantes Inmunológicos , Cíclidos , Enfermedades de los Peces , Inmunidad Innata , Infecciones Estreptocócicas , Streptococcus agalactiae , Animales , Streptococcus agalactiae/inmunología , Infecciones Estreptocócicas/veterinaria , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/inmunología , Cíclidos/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Administración Oral , Alimentación Animal/análisis , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Vacunación/veterinariaRESUMEN
BACKGROUND: Group B streptococcus is a major cause of neonatal disease. Natural history studies have linked maternally transferred anti-group B streptococcus capsular polysaccharide antibodies with protection against infant group B streptococcus disease. Previous studies of capsular polysaccharide antibody concentration in European populations have used maternal (not infant) sera and a non-standardised assay. This study aimed to evaluate anti-capsular polysaccharide IgG concentrations associated with protection against invasive group B streptococcus disease in Finnish infants. METHODS: In this retrospective case-control study, we used cord sera from the Finnish DIPP study repository, which was obtained between Jan 1, 1995, and Dec 31, 2017. We included infants aged 6 months or younger with group B streptococcus infection (cases) and healthy infants (controls). We enrolled infants with invasive neonatal group B streptococcus (55 cases) and matched controls (229 controls) aged 6 months or younger after identification from Finnish health registers. We measured anti-capsular polysaccharide IgG (serotypes Ia-V) concentration using a standardised immunoassay and we estimated its relationship to disease risk using a Bayesian model. We used the derived risk-concentration curve to predict potential efficacy of six-valent group B streptococcus capsular polysaccharide vaccine (GBS6) based on previously reported immunogenicity data. FINDINGS: Most (32 [58%] of 55 cases) group B streptococcus cases were due to serotype III and anti-serotype III streptococcus capsular IgG concentrations were higher in serotype III-matched controls than in cases (p<0·001). 0·120-0·266 µg/mL serotype III-specific IgG was estimated to confer 75-90% risk reduction against serotype III disease. A universal risk-concentration curve, aggregating results across all six serotypes, yielded similar results. Application of this curve to GBS6 immunogenicity data predicted maternal immunisation to be more than 80% efficacious for prevention of infant group B streptococcus disease. INTERPRETATION: Higher neonatal anti-capsular polysaccharide serum IgG concentration at birth correlated with reduced risk of infant group B streptococcus disease in Finland. Based on these results, a maternal group B streptococcus capsular conjugate vaccine currently in development is predicted to be efficacious. FUNDING: Pfizer.
Asunto(s)
Anticuerpos Antibacterianos , Inmunoglobulina G , Infecciones Estreptocócicas , Streptococcus agalactiae , Humanos , Finlandia/epidemiología , Estudios Retrospectivos , Streptococcus agalactiae/inmunología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/sangre , Infecciones Estreptocócicas/epidemiología , Estudios de Casos y Controles , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Femenino , Recién Nacido , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Masculino , Lactante , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Cápsulas Bacterianas/inmunologíaRESUMEN
Superficial infections with Streptococcus pyogenes (Strep A), pharyngitis and impetigo can induce acute rheumatic fever, an autoimmune sequela manifesting mostly with arthritis and rheumatic carditis. Valvular heart damage can persist or advance following repeated episodes of acute rheumatic fever, causing rheumatic heart disease. Acute rheumatic fever and rheumatic heart disease disproportionately affect children and young adults in developing countries and disadvantaged communities in developed countries. People living with rheumatic heart disease are at risk of experiencing potentially fatal complications such as heart failure, bacterial endocarditis or stroke. Transthoracic echocardiography plays a central role in diagnosing both rheumatic carditis and rheumatic heart disease. Despite the obvious medical need, no licensed Strep A vaccines are currently available, as their clinical development process faces several challenges, including concerns for cardiac safety. However, the development of Strep A vaccines has been recently relaunched by many vaccine developers. In this context, a reliable and consistent safety evaluation of Strep A vaccine candidates, including the use of transthoracic echocardiography for detecting cardiac adverse events, could greatly contribute to developing a safe and efficacious product in the near future. Here, we propose a framework for the consistent use of transthoracic echocardiography to proactively detect cardiac safety events in clinical trials of Strep A vaccine candidates.
Throat and skin infections caused by certain types of bacteria, named Streptococcus pyogenes, are frequent worldwide; however, in many children from less developed countries and disadvantaged communities, infections with S. pyogenes lead to a condition called acute rheumatic fever, which usually affects the joints and the heart. Damage to the heart valves may evolve to rheumatic heart disease, a permanent condition with often life-threatening complications. Rheumatic heart disease is an important health problem in places and communities where S. pyogenes infections occur frequently. A vaccine against these bacteria would help lower the number of people with valvular heart disease; however, no such vaccine exists yet. Research on vaccines against S. pyogenes was on hold for almost 30 years because of initial concerns that vaccinated children might develop acute rheumatic fever more frequently. Recently, researchers started working again on vaccines against S. pyogenes, but concerns about the safety of such vaccines persist. Doctors can reliably use echocardiography to diagnose cases of rheumatic carditis (as a sign of acute rheumatic fever) and rheumatic heart disease. Here, we propose a simple approach for the consistent use of echocardiography in clinical research of vaccines against S. pyogenes that will allow the detection of any potential heart-related side effects of the vaccine.
Asunto(s)
Ecocardiografía , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus pyogenes , Humanos , Streptococcus pyogenes/inmunología , Ecocardiografía/métodos , Vacunas Estreptocócicas/administración & dosificación , Vacunas Estreptocócicas/efectos adversos , Vacunas Estreptocócicas/inmunología , Infecciones Estreptocócicas/prevención & control , Cardiopatía Reumática/diagnóstico por imagenRESUMEN
Group B streptococcus (GBS) poses a significant threat to neonates, leading to morbidity and mortality. Intrapartum antibiotics, although effective, have limitations, prompting the exploration of maternal vaccination. This study reviews the current evidence for maternal GBS vaccination in the prevention of early-onset GBS disease in newborns. A search on Google Scholar, PubMed, and Scopus identified studies assessing the impact of maternal GBS vaccination on early-onset GBS disease. Inclusion criteria comprised English-language clinical trials or observational studies. Data extraction included study details, immunogenicity profiles, effectiveness, safety outcomes, and relevant findings. Qualitative synthesis was employed for data analysis. Five studies meeting the inclusion criteria were reviewed. Maternal GBS vaccines demonstrated efficacy with sustained immunogenicity. Adverse events, although documented, were predominantly non-severe. Variability in immune responses and maternal-to-infant antibody ratios show the need for tailored vaccination approaches. Long-term follow up and surveillance are essential to assess persistence and identify unintended effects. Positive outcomes in vaccine efficacy support GBS vaccination integration into maternal health programs. Implementation challenges in diverse healthcare infrastructures require tailored approaches, especially in resource-limited settings. Overcoming cultural barriers and ensuring healthcare provider awareness are crucial for successful vaccination.
Asunto(s)
Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus agalactiae , Humanos , Infecciones Estreptocócicas/prevención & control , Femenino , Recién Nacido , Vacunas Estreptocócicas/administración & dosificación , Vacunas Estreptocócicas/inmunología , Embarazo , Streptococcus agalactiae/inmunología , Complicaciones Infecciosas del Embarazo/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , VacunaciónRESUMEN
BACKGROUND: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants. METHODS: In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies. In a parallel seroepidemiologic study that was conducted in the same population, we assessed serotype-specific anti-CPS IgG concentrations that were associated with a reduced risk of invasive disease among newborns through 89 days of age to define putative protective thresholds. RESULTS: Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study. IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 µg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 µg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation. CONCLUSIONS: GBS6 elicited anti-CPS antibodies against group B streptococcus in pregnant women that were transferred to infants at levels associated with a reduced risk of invasive group B streptococcal disease. (Funded by Pfizer and the Bill and Melinda Gates Foundation; C1091002 ClinicalTrials.gov number, NCT03765073.).
Asunto(s)
Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus agalactiae , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Anticuerpos Antibacterianos , Inmunoglobulina G , Estudios Seroepidemiológicos , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/prevención & control , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunología , Vacunas Combinadas/uso terapéutico , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/uso terapéutico , Vacunas Estreptocócicas/administración & dosificación , Vacunas Estreptocócicas/efectos adversos , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/uso terapéutico , Inmunidad Materno-Adquirida/inmunologíaRESUMEN
A vaccine protecting against different Streptococcus suis serotypes is highly needed in porcine practice to improve animal welfare and reduce the use of antibiotics. We hypothesized that immunogens prominently recognized by convalescence sera but significantly less so by sera of susceptible piglets are putative protective antigens. Accordingly, we investigated immunogenicity and protective efficacy of a multicomponent vaccine including six main conserved immunogens, namely SSU0934, SSU1869, SSU0757, SSU1950, SSU1664 and SSU0187. Flow cytometry confirmed surface expression of all six immunogens in S. suis serotypes 2, 9 and 14. Although prime-booster vaccination after weaning resulted in significantly higher specific IgG levels against all six immunogens compared to the placebo-treated group, no significant differences between bacterial survival in blood from either vaccinated or control animals were recorded for serotype 2, 9 and 14 strains. Furthermore, vaccinated piglets were not protected against morbidity elicited through intranasal challenge with S. suis serotype 14. As ~50% of animals in both groups did not develop disease, we investigated putative other correlates of protection. Induction of reactive oxygen species (ROS) in blood granulocytes was not associated with vaccination but correlated with protection as all piglets with >5% ROS survived the challenge. Based on these findings we discuss that the main immunogens of S. suis might actually not be a priori good candidates for protective antigens. On the contrary, expression of immunogens that evoke antibodies that do not mediate killing of this pathogen might constitute an evolutionary advantage conserved in many different S. suis strains.
Asunto(s)
Inmunogenicidad Vacunal , Infecciones Estreptocócicas/veterinaria , Vacunas Estreptocócicas/inmunología , Streptococcus suis/inmunología , Enfermedades de los Porcinos/prevención & control , Animales , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/administración & dosificación , Sus scrofa , Porcinos , Enfermedades de los Porcinos/microbiología , Resultado del TratamientoRESUMEN
The association of vaccines with immunostimulants such as ß-glucan, promote the production of cytokines, competent immune cells and antibodies. However, differences between ß-glucan types and trials make it difficult to understand ß-glucan's mechanism of action. In this study, three trials were carried out with control and fish fed ß-glucan, the first trial occurred at 15 days; the second trial occurred at 30 days when we associated ß-glucan and vaccine; and the third trial occurred at 15 days post-challenge with Streptococcus agalactiae in tilapia (O. niloticus) in order to investigate immune-related gene expression in the head kidney and spleen using real-time qPCR. We found increases in HSP70, IL-6, IL-1ß, TNF-α, IL-10, Lys and C3 predominantly in the head kidney, except for IgM expression, which prevailed in the spleen, under vaccinated + ß-glucan action. This demonstrates the trade-off presented by the head kidney and spleen after immunostimulation in order to produce acquired immunity, as well as an increase in HSP70 expression in vaccinated + ß-glucan fish. The results suggest that ß-glucan stimulates the immune response through damage-associated molecular patterns (DAMPs) recognition. Therefore, these dynamics of the immune response promote a more robust defense against disease.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Cíclidos/inmunología , Riñón Cefálico/efectos de los fármacos , Bazo/efectos de los fármacos , Vacunas Estreptocócicas/administración & dosificación , beta-Glucanos/administración & dosificación , Inmunidad Adaptativa , Animales , Cíclidos/genética , Cíclidos/microbiología , Citocinas/genética , Enfermedades de los Peces/genética , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/prevención & control , Proteínas de Peces/genética , Expresión Génica/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/genética , Riñón Cefálico/inmunología , Muramidasa/inmunología , Transducción de Señal , Bazo/inmunología , Infecciones Estreptocócicas/genética , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/veterinaria , Streptococcus agalactiaeRESUMEN
Streptococcus equi subspecies equi is a pathogenic bacterium that causes strangles, a highly contagious respiratory infection in horses and other equines. The limitations of current vaccines against S. equi infection warrants the development of an affordable, safe, and effective vaccine. Because gram-positive extracellular vesicles (EVs) transport various immunogenic antigens, they are attractive vaccine candidates. Here, we purified the EVs of S. equi ATCC 39506 and evaluated them as a vaccine candidate against S. equi infection in mice. As an initial step, comparative proteomic analysis was performed to characterize the functional features of the EVs. Reverse vaccinology and knowledge-based annotations were then used to screen potential vaccine candidates (PVCs) for S. equi ATCC 39506. Finally, 32 PVCs were found to be enriched in the EV fraction, suggesting the usefulness of this fraction as a vaccine. Importantly, a significantly higher survival rate after S. equi infection was detected in mice immunized with S. equi-derived EVs via the intraperitoneal route than in mice immunized with heat-killed bacteria. Of note, immunoprecipitation-mass spectrometry results validated various immunogenic antigens within the EV proteome. In conclusion, our results suggest that S. equi-derived EVs can serve as a vaccine candidate against S. equi infection.
Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Vesículas Extracelulares/inmunología , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/inmunología , Streptococcus equi/inmunología , Animales , Antígenos Bacterianos/administración & dosificación , Antígenos Bacterianos/análisis , Proteínas Bacterianas/administración & dosificación , Proteínas Bacterianas/análisis , Vesículas Extracelulares/química , Femenino , Enfermedades de los Caballos/microbiología , Enfermedades de los Caballos/prevención & control , Caballos , Inmunoprecipitación , Espectrometría de Masas/métodos , Ratones , Ratones Endogámicos BALB C , Proteómica , Infecciones Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , VacunaciónRESUMEN
Streptococcus agalactiae is one of the most important pathogens infecting tilapia worldwide and causes meningoencephalitis, septicemia and high mortalities with considerable losses. Various types of vaccines have been developed against S. agalactiae infection, such as inactivated vaccines, live attenuated vaccines and subunit vaccines. Bacterial ghosts (BGs) are nonliving, empty cell envelopes and have been reported as novel vaccine candidates. Therefore, the main aims of this study were to develop an S. agalactiae ghost vaccine (SAGV) and to evaluate the immune response and protective effect of SAGV against S. agalactiae with two novel adjuvants, Montanide™ ISA 763B VG and Montanide™ GEL02. Nile tilapia, mean weight 50 g, were divided into four groups as follows; 1) fish injected with PBS as control, 2) fish injected with the SAGV alone; 3) fish injected with the SAGV+Montanide™ ISA 763B VG; and 4) fish injected with SAGV+Montanide™ GEL02. Following vaccination, innate immunity parameters including serum lysozyme, myeloperoxidase, catalase, and bactericidal activity were all significantly enhanced. Moreover, specific serum IgM antibodies were induced and reached their highest level 2-8 weeks post vaccination. Importantly, the relative percent survival of tilapia vaccinated against the SAGV formulated with both adjuvants was 80-93%. Furthermore, the transcription of immune-related genes (IgM, TCRß, IL-1ß, IL-8 and TNFα) were up-regulated in tilapia after vaccination, indicating that both cellular and humoral immune responses were induced by these adjuvanted vaccines. In summary, Montanide™ ISA 763B VG and Montanide™ GEL02 can enhance immunoprotection induced by the SAGV vaccine against streptococcosis, demonstrating that both have value as potential adjuvants of fish vaccines.