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1.
Front Immunol ; 13: 805026, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493462

RESUMO

Despite the relevance of adaptive immunity against equine pathogens antigen-specific T cell responses of horses are not well characterized and the lack of insight into T cell responses hampers the understanding of the pathogeneses of important diseases. In this study we used tetanus toxoid (TT) as a well-defined antigen to characterize antigen-reactive T cells. Six healthy adult horses received a routine booster against tetanus with an immune stimulating complex (ISCOM)-based vaccine and were followed for 28 days. TT-specific serum antibodies were quantified by ELISA and increased in all horses by day 7 after vaccination. CD154 is an established indicator of antigen-reactive T helper cells in other species, but has not been characterized in horses. CD154 detection in equine PBMC by an anti-human CD154 antibody (clone 5C8) was confirmed by Western blots and then applied for flow cytometry. As a common indicator of equine T cell activation, cytokine induction was studied in parallel. T cells were analyzed by multicolor flow cytometry of PBMC after re-stimulation with TT in vitro. Reactive T helper (Th) cells were characterized by increased frequencies of CD4+CD154+ lymphocytes in in vitro TT-re-stimulated PBMC on day 14 after vaccination of the horses compared to pre-vaccination. The majority of all CD154+ cells after TT re-stimulation were CD4+ Th cells, but CD154 was also induced on CD4- cells albeit in lower frequencies. CD154+CD4+ Th cells were enriched in cytokine-expressing cells compared to CD154-CD4+ Th cells. Similar to the CD4+CD154+ frequencies, CD4+IL-4+, CD4+IFN-γ+ and CD4+TNF-α+ were increased after vaccination, but IL-4+ increased later than IFN-γ+ and CD4+TNF-α+, which already exceeded pre-vaccination frequencies on day 7. CD4+CD154+ frequencies correlated positively with those of CD4+IL-4+ (Th2) on day 14, and negatively with CD4+IFN-γ+ induction on day 7, but did not correlate with CD4+TNF-α+ frequencies or TT-specific antibody concentrations. CD154 appears to be a useful marker of antigen-reactive equine Th cells in combination with cytokine expression. The T cell analyses established here with TT can be applied to other antigens relevant for infections or allergies of horses and in horse models for translational research.


Assuntos
Toxoide Tetânico , Tétano , Animais , Anticorpos Antibacterianos , Ligante de CD40 , Citocinas , Cavalos , Interleucina-4 , Leucócitos Mononucleares , Toxoides , Fator de Necrose Tumoral alfa , Vacinação
2.
Hosp Pediatr ; 12(3): e106-e109, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35132433

RESUMO

BACKGROUND: It is well established that young infants have the highest risk of severe pertussis, which often results in hospitalization. Since the 2012 recommendation of administering tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine for every pregnancy, evaluation of pertussis hospitalizations among young infants in the United States has been limited. METHODS: In this ecological study, we used the Kids' Inpatient Database, the largest all-payer pediatric inpatient database in the United States, to study pertussis hospitalizations among infants <1 month of age from 2000 to 2016. RESULTS: The overall rate of pertussis hospitalizations before the Tdap vaccination recommendation was 5.06 per 100 000 infants (95% confidence interval, 4.36-5.76) and 2.15 per 100 000 infants (95% confidence interval, 1.49-2.81) afterward. CONCLUSIONS: This study supports maternal vaccination against pertussis as an important strategy in protecting young infants, and continued evaluation is needed to assess the long-term trends in hospitalization.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Difteria , Tétano , Coqueluche , Criança , Difteria/prevenção & controle , Feminino , Hospitalização , Humanos , Lactente , Gravidez , Tétano/prevenção & controle , Toxoides , Estados Unidos/epidemiologia , Vacinação , Coqueluche/epidemiologia , Coqueluche/prevenção & controle
3.
Iran J Immunol ; 18(4): 292-303, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34931615

RESUMO

BACKGROUND: Pseudomonas aeruginosa is an important opportunistic pathogen, especially in patients with compromised host defense. OBJECTIVE: To prepare the conjugate of detoxified lipopolysaccharide (D-LPS) and exotoxin A toxoid (T-ETA) from P. aeruginosa in gold nanoparticles (Au NPs) in a mice model. METHODS: LPS and ETA were purified from P. aeruginosa PAO1. D-LPS was conjugated withT-ETA via the amidation method. Au NPs were bound to D-LPS-T-ETA conjugate via electrostatic interaction. Mice were immunized with D-LPS, D-LPS-Au NPs, T-ETA, T-ETA-Au NPs, D-LPS-T-ETA, D-LPS-T-ETA-Au NPs, D-LPS-Au NPs+T-ETA-Au NPs, Au NPs, and phosphate-buffered saline (PBS), and specific IgG titers were determined by the ELISA and the whole-cell ELISA methods. Mice in the vaccinated and control groups were exposed to a 2×LD50 of P. aeruginosa and mortality rates were recorded for one week. RESULTS: The results showed that vaccination by D-LPS, D-LPS-Au NPs, T-ETA, T-ETA-Au NPs, D-LPS-T-ETA, D-LPS-T-ETA-Au NPs and D-LPS-Au NPs+T-ETA-Au NPs induced specific IgG. Mice received the D-LPS-T-ETA-Au NPs conjugate showed significant protection against bacterial challenge. CONCLUSION: These data indicate that D-LPS-T-ETA-Au NPs conjugate has a significant immunogenicity potential to be applied as a new vaccine against Pseudomonas infections.


Assuntos
Nanopartículas Metálicas , Infecções por Pseudomonas , Animais , Anticorpos Antibacterianos , Exotoxinas , Ouro , Humanos , Lipopolissacarídeos , Camundongos , Toxoides
4.
Med J Malaysia ; 76(6): 865-869, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34806674

RESUMO

INTRODUCTION: This study aimed to determine the coverage of tetanus toxoid vaccination (TT) among pregnant women in Cambodia, and its association with health services and pregnancy factors. METHODS: A cross-sectional study was conducted by utilising the data from the Cambodia Demographic Health Survey (CDHS). The records of 5901 pregnant women who fulfilled the inclusion criteria were reviewed. Multiple logistic regression was used to identify the association on the influence of health services and pregnancy factors on incomplete TT vaccination while controlling other covariates. Adjusted odds ratio (aOR) and 95% confidence interval (95%CI) was reported. RESULTS: More than one-third of the respondents had incomplete TT vaccination (38.25%, 95%CI: 37.00, 39.48%). Health services as well as pregnancy factors were statistically associated with incomplete TT vaccination such as received antenatal care (ANC) from other health personnel beside midwife (aOR=1.83; 95%CI: 1.49, 2.24), had

Assuntos
Gestantes , Toxoide Tetânico , Adulto , Camboja , Estudos Transversais , Feminino , Humanos , Gravidez , Cuidado Pré-Natal , História Reprodutiva , Toxoides , Vacinação
5.
Anaerobe ; 72: 102465, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34662696

RESUMO

Herd vaccination is an important preventive measure against enterotoxemia in ruminants. Vaccination in goats should be performed every four months, and recent studies have shown that immunity in cattle lasts for less than one year. One of the mechanisms for increasing the duration of the immune response is to use purified toxoids as immunogens. The aim of the present study was to evaluate the humoral response in cattle and goats after vaccination with purified and semi-purified Clostridium perfringens type D epsilon toxoid. The following three different vaccines were used: vaccine 1 (V1), a semi-purified toxoid adsorbed to aluminum hydroxide; vaccine 2 (V2), a purified toxoid adsorbed to aluminum hydroxide; and vaccine (V3), a purified toxoid adsorbed on chitosan microparticles. Groups of cattle (n = 6-7) and goats (n = 6-7) were vaccinated on days 0 and 30, and serum samples for antitoxin titration were collected every 30 days for one-year post-vaccination. Goats were revaccinated on day 360, and their serum was evaluated on days 367 and 374. The antibody peaks ranged between 6.90 and 11.47 IU/mL in cattle and from 1.11 to 4.40 IU/mL in goats. In cattle administered with the V1 and V2 vaccines, we observed that the antibody titers were maintained above 0.2 IU/mL until the end of the experiment. In goats, V2 elicited long-lasting antibodies, and all animals maintained the protective titers for 210 days after the first dose. In conclusion, the purified toxoid vaccine with aluminum hydroxide adjuvant was able to induce strong and long-lasting humoral responses in both species and could be an alternative for improving the immunization schedule against enterotoxemia in goats and cattle.


Assuntos
Toxinas Bacterianas/imunologia , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/microbiologia , Infecções por Clostridium/veterinária , Clostridium perfringens/imunologia , Doenças das Cabras/microbiologia , Doenças das Cabras/prevenção & controle , Toxoides/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Toxinas Bacterianas/administração & dosagem , Toxinas Bacterianas/química , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/química , Vacinas Bacterianas/imunologia , Bovinos , Clostridium perfringens/classificação , Enterotoxemia/prevenção & controle , Cabras , Imunidade Humoral , Imunização , Coelhos
6.
Appl Microbiol Biotechnol ; 105(21-22): 8297-8311, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34609523

RESUMO

Staphylococcus aureus is a serious pathogen unleashing its virulence through several classes of exotoxins such as hemolysins and enterotoxins. In this study, we designed a novel multi-antigen subunit vaccine which can induce innate, humoral and cellular immune responses. Alpha hemolysin, enterotoxins A and B were selected as protective antigens for combining into a triple antigen chimeric protein (HAB). Immunoinformatics analysis predicted HAB protein as a suitable vaccine candidate for inducing both humoral and cellular immune responses. Tertiary structure of the HAB protein was predicted and validated through computational approaches. Docking studies were performed between the HAB protein and mice TLR2 receptor. Furthermore, we constructed and generated recombinant HAB (r-HAB) protein in E. coli and studied its toxicity, immunogenicity and protective efficacy in a mouse model. Triple antigen chimeric protein (r-HAB) was found to be highly immunogenic in mouse as the anti-r-HAB hyperimmune serum was strongly reactive to all three native exotoxins on Western blot. In vitro toxin neutralization assay using anti-r-HAB antibodies demonstrated > 75% neutralization of toxins on RAW 264.7 cell line. Active immunization with r-HAB toxoid gave ~ 83% protection against 2 × lethal dosage of secreted exotoxins. The protection was mediated by induction of strong antibody responses that neutralized the toxins. Passive immunization with anti-r-HAB antibodies gave ~ 50% protection from lethal challenge. In conclusion, in vitro and in vivo testing of r-HAB found the molecule to be nontoxic, highly immunogenic and induced excellent protection towards native toxins in actively immunized and partial protection to passively immunized mice groups. KEY POINTS: • HAB protein was computationally designed to induce humoral and cellular responses. • r-HAB protein was found to be nontoxic, immunogenic and protective in mouse model. • r-HAB conferred protection against lethal challenge in active and passive immunization.


Assuntos
Toxinas Bacterianas , Toxemia , Animais , Anticorpos Antibacterianos , Toxinas Bacterianas/genética , Enterotoxinas , Escherichia coli/genética , Camundongos , Camundongos Endogâmicos BALB C , Staphylococcus aureus , Toxoides
7.
Vaccine ; 39(40): 5991-6003, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34483022

RESUMO

BACKGROUND: Two phase 1/phase 2 studies assessed 2 formulations of investigational bivalent Clostridioides (Clostridium) difficile vaccine (QS-21 adjuvanted toxoid and toxoid-alone) in healthy adults 50-85 years of age. METHODS: The QS-21 adjuvanted toxoid vaccine study randomized subjects 3:1 to 100 µg QS-21-containing C difficile vaccine or placebo administered in a shortened-month (Months 0, 1, 3) or day (Days 1, 8, 30) regimen. The toxoid-alone vaccine study randomized subjects 3:3:1 to receive 100 or 200 µg unadjuvanted C difficile vaccine formulation or placebo in Stages 1 and 2 (sentinel cohorts of different age groups), and 3:1 to receive the selected dose of unadjuvanted C difficile vaccine formulation or placebo in Stage 3 (Days 1, 8, 30). Safety was the primary outcome for both studies. Immunogenicity was determined by measuring serum toxin A- and B-specific neutralizing antibodies. RESULTS: In the day regimen, 10 reports across both studies of grade 3 injection site redness postdose 2 triggered predefined stopping rules. Local reactions in both studies were more common among vaccine versus placebo recipients. Injection site pain predominated and was generally mild in severity. Systemic events were infrequent and generally mild-to-moderate in severity. Adverse events were reported by 50.0%-75.0% and 16.7%-50.0% of subjects in the QS-21 and toxoid-alone studies, respectively. Immune responses peaked around Day 37 (shortened-month regimen) or between Day 15 and Month 2 (day regimen) and remained above baseline throughout follow-up. CONCLUSIONS: Both formulations demonstrated robust immunogenicity. Both studies stopped early due to grade 3 injection site redness postdose 2 of the day regimen; neither formulation progressed to later stage development. Instead, an aluminum hydroxide-containing formulation of the vaccine candidate administered at 0, 1, and 6 months, which was safe and immunogenic in phase 1 and 2 studies, advanced to phase 3 studies.


Assuntos
Clostridioides difficile , Clostridioides , Vacinas Bacterianas , Clostridium , Humanos , Toxoides
8.
Eur J Obstet Gynecol Reprod Biol ; 265: 212-216, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34534737

RESUMO

OBJECTIVE: Pertussis is an important cause of morbidity and mortality in infants under two months of age and these high risk babies are dependent on maternally derived antibodies until completion of their first immunization series. This study aimed to evaluate the vaccine response of late preterm and term newborns as well as their mothers who underwent combined tetanus-diphtheria toxoid and acellular pertussis (Tdap) vaccination during pregnancy. STUDY DESIGN: A total of 70 pregnant women were administered Tdap vaccine (Boostrix®, GSK) between 27 and 33 gestational weeks of pregnancy. The IgG antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) in maternal blood before vaccination and in both maternal and umbilical cord blood after vaccination were evaluated using the in-house ELISA method. The geometric mean concentrations (GMC) and placental transfer ratios of antibodies were measured. RESULTS: Participants' with a mean age of 29.59 ± 4.70 years received Tdap vaccine at an average 28.6 ± 1.31 gestational weeks. Average pre and post vaccination levels of anti-PT IgG GMCs and anti-FHA IgG GMCs were 8.01 IU/ml vs 39.48 IU/ml (p = 0.001) and 122.24 IU/ml vs 183.97 IU/ml (p < 0.001), respectively. The anti-PT and anti-FHA IgG GMCs of cord blood after vaccination was 25.15 IU/ml and 118.77 IU/ml, respectively (p < 0.001 and p = 0.064). Placental transfer ratios of anti-PT ve anti-FHA IgG antibodies were detected as 0.65 and 0.62, respectively. CONCLUSION: Immunization of pregnant women with Tdap at the third trimester results in high maternal and infant antibody levels. Maternal immunization during each pregnancy seems to be the best strategy in revealing the highest maternal and infant antibodies and in narrowing the gap between birth and immune system maturation in infants. Pregnant women in our country should also get the Tdap vaccine during pregnancy especially in the early third trimester.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Tétano , Coqueluche , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Mães , Placenta , Gravidez , Toxoides , Turquia , Coqueluche/prevenção & controle , Adulto Jovem
9.
Toxins (Basel) ; 13(8)2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34437437

RESUMO

In horses, Clostridium perfringens is associated with acute and fatal enterocolitis, which is caused by a beta toxin (CPB), and myonecrosis, which is caused by an alpha toxin (CPA). Although the most effective way to prevent these diseases is through vaccination, specific clostridial vaccines for horses against C. perfringens are not widely available. The aim of this study was to pioneer the immunization of horses with three different concentrations (100, 200 and 400 µg) of C. perfringens recombinant alpha (rCPA) and beta (rCPB) proteins, as well as to evaluate the humoral immune response over 360 days. Recombinant toxoids were developed and applied to 50 horses on days 0 and 30. Those vaccines attempted to stimulate the production of alpha antitoxin (anti-CPA) and beta antitoxin (anti-CPB), in addition to becoming innocuous, stable and sterile. There was a reduction in the level of neutralizing anti-CPA and anti-CPB antibodies following the 60th day; therefore, the concentrations of 200 and 400 µg capable of inducing a detectable humoral immune response were not determined until day 180. In practical terms, 200 µg is possibly the ideal concentration for use in the veterinary industry's production of vaccines against the action of C. perfringens in equine species.


Assuntos
Antígenos de Bactérias/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Infecções por Clostridium/prevenção & controle , Doenças dos Cavalos/prevenção & controle , Toxoides/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Neutralizantes/sangue , Infecções por Clostridium/veterinária , Clostridium perfringens/imunologia , Feminino , Cavalos/imunologia , Imunidade Humoral , Masculino , Proteínas Recombinantes/administração & dosagem , Toxoides/genética , Vacinação
10.
Infect Immun ; 89(10): e0034221, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34227839

RESUMO

In the Gram-positive pathogen Staphylococcus aureus, pore-forming toxins (PFTs), such as leukocidins and hemolysins, play prominent roles in staphylococcal pathogenesis by killing host immune cells and red blood cells (RBCs). However, it remains unknown which combination of toxin antigens would induce the broadest protective immune response against those toxins. In this study, by targeting six major staphylococcal PFTs (i.e., gamma-hemolysin AB [HlgAB], gamma-hemolysin CB [HlgCB], leukocidin AB [LukAB], leukocidin ED [LukED], Panton-Valentine leukocidin [LukSF-PV], and alpha-hemolysin [Hla]), we generated 10 recombinant toxins or toxin subunits, 3 toxoids, and their rabbit antibodies. Using the cytolytic assay for RBCs and polymorphonuclear cells (PMNs), we determined the best combination of toxin antibodies conferring the broadest protection against those staphylococcal PFTs. Although anti-HlgA IgG (HlgA-IgG) showed low cross-reactivity to other toxin components, it was essential to protect rabbit and human RBCs and human PMNs. For the protection of rabbit RBCs, HlaH35L toxoid-IgG was also required, whereas for human PMNs, LukS-IgG and LukAE323AB-IgG were essential too. When the toxin/toxoid antigens HlgA, LukS-PV, HlaH35L, and LukAE323AB were used to immunize rabbits, they increased rabbit survival; however, they did not block staphylococcal abscess formation in kidneys. Based on these results, we proposed that the combination of HlgA, LukS, HlaH35L, and LukAE323AB is the optimal vaccine component to protect human RBCs and PMNs from staphylococcal PFTs. We also concluded that a successful S. aureus vaccine requires not only those toxin antigens but also other antigens that can induce immune responses blocking staphylococcal colonization.


Assuntos
Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Vacinas Combinadas/imunologia , Animais , Proteínas de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Reações Cruzadas/imunologia , Eritrócitos/imunologia , Eritrócitos/microbiologia , Exotoxinas/imunologia , Proteínas Hemolisinas/imunologia , Humanos , Imunização/métodos , Leucocidinas/imunologia , Neutrófilos/imunologia , Neutrófilos/microbiologia , Coelhos , Infecções Estafilocócicas/microbiologia , Toxoides/imunologia
11.
Am J Case Rep ; 22: e933003, 2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34304240

RESUMO

BACKGROUND It is unknown if the efficacy of the coronavirus disease-19 (COVID-19) vaccine is affected by the co-administration of other vaccines. The Centers for Disease Control and Prevention (CDC) has shifted their recommendations recently, allowing for the co-administration of the currently available COVID-19 vaccines with other vaccines. This is based on the experience with non-COVID-19 vaccines, where the immunogenicity and adverse event profiles were generally similar when vaccines are administered simultaneously or alone. CASE REPORT We present a case of a 29-year-old Asian woman who received the first dose of BNT162b2 mRNA vaccine and the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine at around the same time. BNT162b2 mRNA vaccine and Tdap vaccine were administered into the deltoid region of the left arm and right arm, respectively. We then monitored for immunogenicity. We observed a delay in the development of SARS-CoV-2 Spike (S1) protein antibodies at around 8 weeks after the second dose. CONCLUSIONS Unless warranted, it is important to adhere to current CDC recommendations with regards to the co-administration of vaccines. Although the administration of Tdap with COVID-19 vaccine in our case caused delay in immunogenicity, it did not negate the ability of the BNT162B2 mRNA vaccine to elicit an adequate immune response. The reason for delay in immune response with co-administration of COVID-19 vaccines with other vaccines is unknown and further studies are needed.


Assuntos
COVID-19 , Vacinas contra Difteria, Tétano e Coqueluche Acelular , Adulto , Anticorpos Antibacterianos , Vacinas contra COVID-19 , Feminino , Humanos , RNA Mensageiro , SARS-CoV-2 , Toxoides
12.
Vaccine ; 39(13): 1818-1825, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33678453

RESUMO

Persistence of immune memory in humans is a crucial yet poorly understood aspect of immunology. Here we have studied the effect of Puumala hantavirus infection on unrelated, pre-existing immune memory by studying T cell- and antibody responses against toxoid vaccine antigens of diphtheria, tetanus and pertussis in a cohort of 45 patients. We found that tetanus- and pertussis -specific IgG concentrations elevate during acute Puumala virus infection. Increase in vaccine IgG was associated with proliferation of heterologous T cells. Interestingly, increases in tetanus-specific IgG persisted a year after the infection while pertussis-specific IgG declined rapidly; a difference in IgG kinetics resembling the difference seen after vaccination against tetanus and pertussis. These results suggest that persistence of immune memory is facilitated by heterologous boosting of old memory during memory formation against newly encountered antigens. They also show that different toxoid antigens may be treated differently. Our study gives new insight into how immune memory formation may alter pre-existing immune memory, and also shows that heterologous immunity may have an impact on vaccination outcomes.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Difteria , Tétano , Coqueluche , Anticorpos Antibacterianos , Vacina contra Difteria, Tétano e Coqueluche , Humanos , Toxoide Tetânico , Toxoides
13.
Jpn J Infect Dis ; 74(5): 399-404, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33518629

RESUMO

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is generally used for booster vaccination of infants in Europe and the United States to avoid increased reactogenicity after diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccination. However, Japan has extended the use of additional DTaP vaccination without reducing the antigen dose for diphtheria and pertussis in adolescents and adults, despite limited reports on its safety in adults. This prospective, observational, questionnaire-based study investigated the occurrence of adverse events (AEs) following DTaP vaccination between June 2018 and June 2019 in participants aged 10 years or older. Of the 250 eligible participants, 235 (94%) responded regarding AEs. Among them, 133 (56.6%) reported AEs, of which 39 reported systemic AEs (16.6%) and 120 reported local AEs (51.1%) attributed to DTaP vaccination. The incidence of local AEs was markedly higher with DTaP vaccination than with non-DTaP vaccination (51.1% vs. 10.5%), and AEs appeared later (P < 0.01) and lasted longer (P < 0.01) with DTaP vaccination. However, more than 75% of these AEs resolved within 7 days. DTaP vaccination was not associated with any serious AEs. These results indicate that the DTaP vaccine can be widely used as a booster in adults as an alternative to the Tdap vaccine.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Vacinas contra Difteria, Tétano e Coqueluche Acelular/efeitos adversos , Difteria/prevenção & controle , Tétano/prevenção & controle , Toxoides/efeitos adversos , Coqueluche/prevenção & controle , Adolescente , Adulto , Anticorpos Antibacterianos , Difteria/epidemiologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Humanos , Imunização Secundária , Incidência , Lactente , Japão/epidemiologia , Masculino , Estudos Prospectivos , Toxoides/administração & dosagem , Coqueluche/epidemiologia
14.
Anaerobe ; 69: 102326, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33508438

RESUMO

Beta toxins (CPB) produced by Clostridium perfringens type B and C cause various diseases in animals, and the use of toxoids is an important prophylactic measure against such diseases. Promising recombinant toxoids have been developed recently. However, both soluble and insoluble proteins expressed in Escherichia coli can interfere with the production and immunogenicity of these antigens. In this context, bioinformatics tools have been used to design new versions of the beta toxin, and levels of expression and solubility were evaluated in different strains of E. coli. The immunogenicity in sheep was assessed using the molecule with the greatest potential that was selected on analyzing these results. In silico analyzes, greater mRNA stability (-169.70 kcal/mol), solubility (-0.755), and better tertiary structure (-0.12) were shown by rCPB-C. None of the strains of E. coli expressed rFH8-CPB, but a high level of expression and solubility was shown by rCPB-C. Higher levels of total and neutralizing anti-CPB antibodies were observed in sheep inoculated with bacterins containing rCPB-C. Thus, this study suggests that due to higher productivity of rCPB-C in E. coli and immunogenicity, it is considered as the most promising molecule for the production of a recombinant vaccine against diseases caused by the beta toxin produced by C. perfringens type B and C.


Assuntos
Anticorpos Neutralizantes/farmacologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Clostridium perfringens/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Toxoides/farmacologia , Vacinas Sintéticas/farmacologia , Animais , Imunogenicidade da Vacina , Ovinos
15.
MAbs ; 13(1): 1869406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33427589

RESUMO

Due to their shared genetic history, antibodies from the same clonotype often bind to the same epitope. This knowledge is used in immune repertoire mining, where known binders are used to search bulk sequencing repertoires to identify new binders. However, current computational methods cannot identify epitope convergence between antibodies from different clonotypes, limiting the sequence diversity of antigen-specific antibodies that can be identified. We describe how the antibody binding site, the paratope, can be used to cluster antibodies with common antigen reactivity from different clonotypes. Our method, paratyping, uses the predicted paratope to identify these novel cross clonotype matches. We experimentally validated our predictions on a pertussis toxoid dataset. Our results show that even the simplest abstraction of the antibody binding site, using only the length of the loops involved and predicted binding residues, is sufficient to group antigen-specific antibodies and provide additional information to conventional clonotype analysis. Abbreviations: BCR: B-cell receptor; CDR: complementarity-determining region; PTx: pertussis toxoid.


Assuntos
Anticorpos/imunologia , Antígenos/imunologia , Sítios de Ligação de Anticorpos/imunologia , Biologia Computacional/métodos , Software , Toxoides/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Células Clonais/imunologia , Regiões Determinantes de Complementaridade/imunologia , Células HEK293 , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Camundongos , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Análise de Célula Única/métodos
16.
Vaccine ; 39(11): 1652-1660, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532546

RESUMO

Pneumolysin is a highly conserved, cholesterol-dependent cytolysin that is an important Streptococcus pneumoniae virulence factor and an attractive target for vaccine development. To attenuate pneumolysin toxicity, a genetic toxoid was constructed with two amino acid changes, G293S and L460D, termed PLY-D, that reduced cytolytic activity > 125,000-fold. In mice, PLY-D elicited high anti-PLY IgG antibody titers that neutralized the cytolytic activity of the wild-type toxin in vitro. To evaluate the protective efficacy of PLY-D, mice were immunized intramuscularly and then challenged intranasally with a lethal dose of 28 clinical isolates of S. pneumoniae originating from different geographical locations, disease states (i.e. bacteremia, pneumonia), or body sites (i.e. sputum, blood). PLY-D immunization conferred significant protection from challenge with 17 of 20 serotypes (85%) and 22 of 28 strains (79%). Further, we demonstrated that immunization with PLY-D provided statistically significant improvement in survival against challenge with serotype 4 and 18C strains compared to mice immunized with a pneumococcal conjugate vaccine Prevnar 13® (PCV13). Co-administration of PLY-D and PCV13 conferred greater protection against challenge with a serotype 6B strain than immunization with either vaccine alone. These data indicate that PLY-D is a broadly protective antigen with the potential to serve as a serotype-independent vaccine against invasive pneumococcal disease either alone or in combination with PCVs.


Assuntos
Infecções Pneumocócicas , Toxoides , Animais , Proteínas de Bactérias/genética , Camundongos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Streptococcus pneumoniae , Estreptolisinas
18.
Innate Immun ; 27(1): 89-98, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33317363

RESUMO

The human pathogen Bordetella pertussis targets the respiratory epithelium and causes whooping cough. Its virulence factor adenylate cyclase toxin (CyaA) plays an important role in the course of infection. Previous studies on the impact of CyaA on human epithelial cells have been carried out using cell lines derived from the airways or the intestinal tract. Here, we investigated the interaction of CyaA and its enzymatically inactive but fully pore-forming toxoid CyaA-AC- with primary human airway epithelial cells (hAEC) derived from different anatomical sites (nose and tracheo-bronchial region) in two-dimensional culture conditions. To assess possible differences between the response of primary hAEC and respiratory cell lines directly, we included HBEC3-KT in our studies. In comparative analyses, we studied the impact of both the toxin and the toxoid on cell viability, intracellular cAMP concentration and IL-6 secretion. We found that the selected hAEC, which lack CD11b, were differentially susceptible to both CyaA and CyaA-AC-. HBEC3-KT appeared not to be suitable for subsequent analyses. Since the nasal epithelium first gets in contact with airborne pathogens, we further studied the effect of CyaA and its toxoid on the innate immunity of three-dimensional tissue models of the human nasal mucosa. The present study reveals first insights in toxin-cell interaction using primary hAEC.


Assuntos
Toxina Adenilato Ciclase/toxicidade , Toxinas Bacterianas/toxicidade , Bordetella pertussis/enzimologia , Adulto , Idoso , Antígeno CD11b/genética , Linhagem Celular , Sobrevivência Celular , Células Epiteliais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/citologia , Mucosa Nasal/efeitos dos fármacos , Cultura Primária de Células , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Toxoides/farmacologia , Coqueluche
19.
Arch Razi Inst ; 75(3): 385-395, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33025779

RESUMO

Toxoid vaccines can provide protective immunity against clostridial diseases. Since the duration of the toxoid vaccine immunogenicity is short, these vaccines need to contain an adjuvant. The nanoparticles of chitosan can stimulate humoral and cell-mediated immune responses. In the present study, the effect of chitosan nanoparticles was investigated on the immunogenicity of the pentavalent clostridial toxoid vaccine containing Clostridium perfringens types D, C, and B, Clostridium septicum, as well as Clostridium novyi. Rabbits were immunized by two injections with 3-week intervals and checked clinically and through autopsy 2 weeks after the last injection. Hematological changes were investigated during immunization, including the changes of white and red blood cell counts, hemoglobin, packed cell volume, platelet, neutrophil, lymphocyte, eosinophil, basophile, monocyte, and Neut/Lymph. Biochemical factors, namely creatinine, blood urea nitrogen, glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and albumin, were also studied. The changes in immune responses during the immunization period were investigated through indirect enzyme-linked immunosorbent assay (ELISA). The results of ELISA showed that chitosan significantly enhanced immunogenicity when accompanied with in the pentavalent clostridial toxoid vaccine. During the immunogenicity period and following that, no changes were observed in clinical behavior and internal organs after autopsy. The hematological and biochemical factors were reported with no significant pathologic changes during immunization in the control and vaccinated groups (p &lt;0.05). The obtained findings revealed that the toxoid vaccines could not induce significant physiological changes in the body. The vaccine containing chitosan could stimulate humoral immunity 2-3 times higher than the nonchitosan vaccine. The humoral immune response was significantly duplicated due to the chitosan effect. Chitosan not only had no local or general side effects but also could be a good help with the enhancement of the immune system; therefore, it can be recommended as an appropriate safe adjuvant in the development of toxoid vaccines.


Assuntos
Vacinas Bacterianas/imunologia , Quitosana/imunologia , Clostridium perfringens/imunologia , Clostridium septicum/imunologia , Clostridium/imunologia , Nanopartículas/administração & dosagem , Vacinas Combinadas/imunologia , Quitosana/administração & dosagem , Imunogenicidade da Vacina/imunologia , Toxoides/imunologia
20.
Pesqui. vet. bras ; 40(10): 776-780, Oct. 2020. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1143413

RESUMO

Clostridium perfringens is considered one of the main causative agents of superacute enterocolitis, usually fatal in the equine species, due to the action of the ß toxin, and is responsible for causing severe myonecrosis, by the action of the α toxin. The great importance of this agent in the equine economy is due to high mortality and lack of vaccines, which are the main form of prevention, which guarantee the immunization of this animal species. The aim of this study was to evaluate three different concentrations (100, 200 and 400µg) of C. perfringens α and ß recombinant toxoids in equine immunization and to compare with a group vaccinated with a commercial toxoid. The commercial vaccine was not able to stimulate an immune response and the recombinant vaccine was able to induce satisfactory humoral immune response in vaccinated horses, proving to be an alternative prophylactic for C. perfringens infection.(AU)


Clostridium perfringens é considerado um dos principais agentes causadores de enterocolites superagudas, geralmente fatais na espécie equina, devido à ação da toxina ß, além de ser responsável por causar quadros graves de mionecrose, pela ação da toxina α. A grande importância desses agentes na equinocultura, deve-se a elevada mortalidade e a inexistência de vacinas, principal forma de prevenção, que garantam a imunização dessa espécie animal. O objetivo deste trabalho foi avaliar três diferentes concentrações (100, 200 e 400µg) dos toxóides recombinantes α e ß de C. perfringens na imunização de equinos, bem como comparar com um grupo vacinado com um toxóide comercial. A vacina comercial não se mostrou capaz de estimular uma resposta imune e a vacina recombinante foi capaz de induzir resposta imune humoral satisfatória em equinos vacinados, provando ser uma alternativa profilática para infecção por C. Perfringens.(AU)


Assuntos
Animais , Toxoides , Enterocolite Pseudomembranosa/veterinária , Vacinas Sintéticas/uso terapêutico , Clostridium perfringens/imunologia , Gangrena Gasosa/veterinária , Cavalos , Imunização/veterinária
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