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1.
Anal Chem ; 93(40): 13580-13588, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34596381

RESUMO

Arrayed imaging reflectometry (AIR) is an optical biosensor platform for simple, multiplex measurement of antigen-specific antibody responses in patient blood samples. Here, we report the development of StaphAIR, an 8-plex Staphylococcus aureus antigen array on the AIR platform for profiling antigen-specific anti-S. aureus humoral immune responses. Initial validation experiments with mouse and humanized monoclonal antibodies against the S. aureus autolysin glucosaminidase (Gmd) domain, and subsequent testing with dilution series of pooled positive human serum confirmed analytically robust behavior of the array, with all antigens displaying Langmuir-type dose-response curves. Testing a cohort of 82 patients with S. aureus musculoskeletal infections (MSKI) and 30 healthy individuals enabled discrimination of individual patient responses to different S. aureus antigens, with statistical significance between osteomyelitis patients and controls obtained overall for four individual antigens (IsdA, IsdB, Gmd, and SCIN). Multivariate analyses of the antibody titers obtained from StaphAIR revealed its utility as a potential diagnostic tool for detecting S. aureus MSKI (area under the receiver operating characteristic curve (AUC) > 0.85). We conclude that StaphAIR has utility as a high-throughput immunoassay for studying and diagnosing osteomyelitis in patients.


Assuntos
Osteomielite , Infecções Estafilocócicas , Animais , Anticorpos Antibacterianos , Formação de Anticorpos , Humanos , Camundongos , Osteomielite/diagnóstico , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus
2.
Mymensingh Med J ; 30(4): 967-972, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34605464

RESUMO

Scrub typhus, caused by the bacterium- Orientia tsutsugamushi is one of the leading causes of undifferentiated treatable febrile illness in Asia pacific region. It is grossly under diagnosed in many tropical countries of South Asia including Bangladesh, due to wide range of non-specific clinical presentations, low index of suspicion among clinicians, limited awareness and lack of accurate diagnostic facilities. This cross-sectional descriptive study was conducted at Department of Microbiology, Mymensingh Medical College to diagnose scrub typhus by rapid Immunochromatographic test (ICT) as well as molecular detection of O. tsutsugamushi by Nested PCR and automated nucleotide sequencing among suspected febrile patients in Mymensingh, Bangladesh during 2019-20. Blood samples were collected from 402 febrile patients of suspected Rickettsial illness, referred from inpatient and outpatient departments of Medicine and Pediatrics, Mymensingh Medical College Hospital (MMCH). Among the enrolled 402 patients, 89 samples (22.13%) were seropositive by Immunochromatographic test (ICT) and 65 samples (16.16%) were positive for O. tsutsugamushi DNA by Nested PCR, targeting 47KDa gene. Therefore, 113/402 (28.10%) samples were positive for scrub typhus by PCR and/ or ICT. Highest number of patients was detected positive by nested PCR during the first 5-10 days of fever but only 2 cases were positive after 20 days. In case of ICT, highest positivity for only IgM (8.13%) and both antibodies (2.43%) were documented in first 5-10 days of fever, but IgG positivity was highest (41.66) in >20 days of fever. From 65 PCR positive samples, automated nucleotide sequencing was performed on 20 randomly selected samples and all were genetically confirmed to be O. tsutsugamushi.


Assuntos
Tifo por Ácaros , Anticorpos Antibacterianos , Criança , Estudos Transversais , Hospitais , Humanos , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/epidemiologia , Sensibilidade e Especificidade
3.
BMC Infect Dis ; 21(1): 897, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479491

RESUMO

BACKGROUND: Maternal immunization confers passive immunity to the fetus by transplacental antibody transfer. Infants may be better protected against pertussis if the mother received a diphtheriae, tetanus and acellular pertussis (Tdap) vaccination in the second trimester of pregnancy compared to the third trimester. This study evaluates IgG antibody concentrations in term and preterm infants at birth and 2 months after birth after maternal Tdap-vaccination between 200 and 240 w of gestation vs third trimester Tdap-vaccination. Further aims are assessing the determinants that underlie acceptance of second trimester maternal Tdap-vaccination as well as the tolerability of vaccination. METHODS: This prospective cohort study consists of two parts. In the acceptance part, pregnant women complete a questionnaire on determinants that underlie acceptance of a second trimester Tdap-vaccination, which is offered subsequently between 200 and 240 w of gestation. Vaccinated women complete an additional questionnaire on vaccination tolerability. Vaccinated women may also participate in the immunogenicity part, in which blood is drawn from mother at delivery and from infant at birth and 2 months after birth. Women are also eligible for the immunogenicity part if they received a Tdap-vaccination between 200 and 240 w of gestation via the national immunization program and get hospitalized for an imminent preterm delivery. Blood sampling continues until 60 term and 60 preterm mother-infant-pairs have been included. Pertussis-specific IgG antibody concentrations are determined in serum using a fluorescent bead-based multiplex immunoassay. For term infants, non-inferiority in IgG antibody concentrations against pertussis toxin (anti-PT) will be assessed referred to a historical control group in which mothers were Tdap-vaccinated between 300 and 320 w of gestation. For preterm infants, non-inferiority of anti-PT IgG concentrations is referred to as 85% of infants having ≥ 20 international units/mL at 2 months after birth. DISCUSSION: This study investigates acceptance, tolerability and immunogenicity regarding maternal Tdap-immunization between 200 and 240 w of gestation. Its results provide insight into the effects of second trimester Tdap-vaccination on IgG antibody concentrations in term and preterm infants before primary infant vaccinations. Results on acceptance and tolerability guide antenatal care providers in communication with pregnant women and maintain the safety of second trimester Tdap-vaccination. TRIAL REGISTRATION: EU Clinical Trials Register, 2018-002976-41, retrospectively registered 24 July 2019, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-002976-41 .


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Coqueluche , Anticorpos Antibacterianos , Estudos de Coortes , Feminino , Humanos , Imunização , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Vacinação , Coqueluche/prevenção & controle
4.
Anal Chem ; 93(36): 12426-12433, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34470214

RESUMO

The detection of IgG/IgM antibodies is a crucial tool for the diagnosis of infectious diseases as they give specific information such as the stage of infection or when it approximately occurred. In this work, a linear cryogel array (LCA) technology is described for the detection of IgG and IgM antibodies, indicative of a borreliosis infection in human sera. The LCA consists of a transparent capillary filled with functionalized cryogel compartments. For the generation of these cryogel arrays, solutions containing a photo-copolymer and the appropriate antigens are sucked into a surface-modified glass capillary. The solution compartments are separated from each other through air pockets. After freezing the solutions, a photo-induced cross-linking process is performed, through which the solutions are transformed into cryogel compartments, covalently attached to the capillary walls. We show that the LCA technology allows the simultaneous detection of IgG and IgM antibodies via a sandwich immunoassay in sera from Borrelia-infected patients within 1 h for sample sizes of only 12 µL. A study with sera from 42 patients conducted with the LCAs and referenced - depending on the source of the sera - to a commercial line immunoassay and a chemiluminescent immunoassay, which are currently widely used for Lyme disease screening, demonstrates the diagnostic potential of the approach.


Assuntos
Criogéis , Doença de Lyme , Anticorpos Antibacterianos , Humanos , Imunoglobulina M , Doença de Lyme/diagnóstico , Sensibilidade e Especificidade
5.
Vaccine ; 39(41): 6067-6073, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34511302

RESUMO

BACKGROUND: In the context of reported resurgence of pertussis in the last decade, researchers hypothesized that acellular (aP) pertussis vaccines elicit a shorter-lived protection compared to whole-cell (wP) pertussis vaccines. However, in the studies seeking to demonstrate this hypothesis, exposure to each vaccine type was not concurrent, and contradictory epidemiologic modeling questioned its validity. The context of pertussis vaccination history in Poland, with both vaccine types used concurrently in comparable proportions, provided an opportunity to investigate this hypothesis. We sought to compare waning of protection by primary series vaccine type by measuring anti-pertussis toxin antibody concentrations as proxy for recent infection. MATERIALS AND METHODS: Serological samples from 2,745 children and adolescents aged ≥5 years and <16 years and with completed 5-dose pertussis vaccination series were tested by ELISA for pertussis toxin (PT) antibodies. Participants were stratified by type of priming vaccine (wP or aP). Vaccination timeliness and priming-specific trends in anti-PT antibody levels by time since last vaccine dose were analyzed. RESULTS: A total of 1,161 (42.5%) children received wP vaccines, and 1,314 (48.1%) received aP vaccines for their primary series and toddler booster. Overall, 53.57% of the subjects received doses 2-4 in a timely manner, while only 41.52% received all 5 doses at the recommended intervals. Using GMCs or seropositivity measures, both priming groups showed a re-increase in anti-PT antibody levels signing infection in recent years from 8 years after the school-entry booster onward. Comparisons did not show any significant differences between the two groups in the timing or intensity of this re-increase. CONCLUSION: Our results clearly confirm that vaccine-elicited immunity against pertussis wanes among adolescents even after a complete infant, toddler and school-entry vaccination series. The timing and intensity of the waning of protection appear similar with whole-cell as with acellular pertussis vaccines.


Assuntos
Bordetella pertussis , Coqueluche , Adolescente , Anticorpos Antibacterianos , Humanos , Imunização Secundária , Vacina contra Coqueluche , Polônia , Vacinas Acelulares , Coqueluche/prevenção & controle
6.
Mater Sci Eng C Mater Biol Appl ; 128: 112316, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474867

RESUMO

To develop a nanoparticle-based vaccine against necrotic enteritis, a chimeric antigen (rNA) consisting of the main antigens of Clostridium perfringens, NetB, and Alpha toxin, was prepared. Then, the rNA molecules were loaded onto the functionalized mesoporous silica nanoparticles (MSNPs) using physical adsorption or covalent conjugation methods. The characterization of synthesized nanoparticles was performed by scanning electron microscopy, dynamic light scattering, zeta potential measurement, Fourier transform infrared spectroscopy, and thermogravimetry techniques. The results revealed that the spherical nanoparticles with an average diameter of 90 ±â€¯12 nm and suitable surface chemistries are prepared. MSNPs-based formulations did not show any significant toxicity on the chicken embryo fibroblast cells. The results of the challenge experiments using subcutaneous or oral administration of the as-prepared formulations in the animal model showed that the as-prepared nanosystems, similar to those formulated with a commercial adjuvant (Montanide), present stronger humoral immune responses as compared to that of the free proteins. It was also indicated that the best protection is obtained in groups vaccinated with MSNPs-based nanovaccine, especially those who orally received covalently conjugated nanovaccine candidates. These results recommend that the MSNPs-based formulated chimeric proteinous vaccine candidates can be considered as an effective immunizing system for the oral vaccination of poultry against gastrointestinal infectious diseases.


Assuntos
Toxinas Bacterianas , Infecções por Clostridium , Enterite , Nanopartículas , Doenças das Aves Domésticas , Vacinas , Animais , Anticorpos Antibacterianos , Embrião de Galinha , Galinhas , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Enterite/prevenção & controle , Enterite/veterinária , Doenças das Aves Domésticas/prevenção & controle , Dióxido de Silício
7.
MAbs ; 13(1): 1978130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34586015

RESUMO

Recent years have seen unparalleled development of microfluidic applications for antibody discovery in both academic and pharmaceutical research. Microfluidics can support native chain-paired library generation as well as direct screening of antibody secreting cells obtained by rodent immunization or from the human peripheral blood. While broad diversities of neutralizing antibodies against infectious diseases such as HIV, Ebola, or COVID-19 have been identified from convalescent individuals, microfluidics can expedite therapeutic antibody discovery for cancer or immunological disease indications. In this study, a commercially available microfluidic device, Cyto-Mine, was used for the rapid identification of natively paired antibodies from rodents or human donors screened for specific binding to recombinant antigens, for direct screening with cells expressing the target of interest, and, to our knowledge for the first time, for direct broad functional IgG antibody screening in droplets. The process time from cell preparation to confirmed recombinant antibodies was four weeks. Application of this or similar microfluidic devices and methodologies can accelerate and enhance pharmaceutical antibody hit discovery.


Assuntos
Anticorpos Neutralizantes/isolamento & purificação , Imunoglobulina G/isolamento & purificação , Microfluídica/métodos , Animais , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/isolamento & purificação , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/isolamento & purificação , Especificidade de Anticorpos , Antígenos/imunologia , Antígenos de Neoplasias/imunologia , Preservação de Sangue , COVID-19/imunologia , Transferência Ressonante de Energia de Fluorescência , Humanos , Hibridomas/imunologia , Separação Imunomagnética , Dispositivos Lab-On-A-Chip , Camundongos , Microfluídica/instrumentação , Muromonab-CD3/imunologia , Plasmócitos , Proteínas Recombinantes/imunologia , SARS-CoV-2/imunologia , Toxoide Tetânico/imunologia , Vacinação
8.
Braz J Biol ; 83: e246385, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34524372

RESUMO

Coronary heart disease (CHD) has been associated with significant morbidity and mortality worldwide. Although remain controversial, several studies have demonstrated the association of M. pneumoniae infections with atherosclerosis. We evaluated the possible association of mycoplasma infections in patients diagnosed with atherosclerosis by ELISA and PCR methods. Atherosclerotic tissue samples and blood samples were collected for the detection of mycoplasma antibodies (IgA) by ELISA from the 97 patients with coronary artery disease (CAD). M. pneumoniae specific IgA, IgG and IgM were measured by using the Anti-M. pneumoniae IgA/IgG/IgM ELISA. Detection of M. pneumoniae targeting the P1 adhesion gene was performed by PCR Acute infection of M. pneumoniae was diagnosed in 43.3% (42) of patients by PCR. The M. pneumoniae specific antibodies were detected in 36.1% (35) of patients. Twenty-five (25.8%) cases had IgG antibodies, 15 (15.5%) cases had IgM antibodies, 3 (3.1%) cases had IgA antibodies, 10 (10.3%) cases had both IgM + IgG antibodies and 1 (1%) case of each had IgM + IgA and IgG + IgA antibodies. None of the cases was positive for all three antibodies. A Pearson correlation coefficient analysis revealed an excellent correlation between the PCR and the serological results (r=0.921, p<0.001). A majority (17, 40.5%) of the M. pneumoniae positive patients are within the 41-50 years of age group, followed by 10 (23.8%) patients in the age group of 61-70 years and 2 (4.8%) patients were >70 years of age. Our study reported an unusually higher prevalence of M. pneumoniae by serological tests (36.1%) and PCR (43.3%). Although the hypothesis of the association of M. pneumoniae and CAD is yet to be proven, the unusually high prevalence of M. pneumoniae in CAD patients indicates an association, if not, in the development of atherosclerosis.


Assuntos
Doença da Artéria Coronariana , Infecções por Mycoplasma , Adulto , Idoso , Anticorpos Antibacterianos , Doença da Artéria Coronariana/epidemiologia , Humanos , Imunoglobulina M , Pessoa de Meia-Idade , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/epidemiologia , Mycoplasma pneumoniae , Prevalência
9.
J Pharm Biomed Anal ; 205: 114340, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34474230

RESUMO

Burkholderia pseudomallei causes melioidosis - an infectious disease with high mortality. Its varied clinical manifestations and resistance to many antibiotics make it a potential biothreat agent and calls for a robust diagnostic assay and effective vaccines. Bacterial cell surface polysaccharides are considered a valuable target for diagnostics and as protective antigen candidates. This study characterized the structure of polysaccharides of B. pseudomallei clinical strain from Hainan, China. A novel structural domain [→3-(α-D-Manp-1→3-α-D-Manp)2-2Me-α-L-6dTalp-1→] was identified by chemical analysis, gas chromatography-mass spectrometry (GC-MS), and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Immunofluorescence and enzyme-linked immunosorbent assay (ELISA) showed that the serum antibodies against the purified polysaccharide antigen could recognize and bind specifically to B. pseudomallei strains. Additionally, the assays revealed cross-reactivity with polysaccharides from different clinical strains. The polysaccharide antigen also exhibited a strong reaction with the sera from melioidosis patients. Thus, the pentasaccharide repeating unit residue could be a potential candidate antigen for the melioidosis serodiagnosis and vaccine development.


Assuntos
Burkholderia pseudomallei , Melioidose , Anticorpos Antibacterianos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Melioidose/diagnóstico , Polissacarídeos Bacterianos
10.
J S Afr Vet Assoc ; 92(0): e1-e7, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34476956

RESUMO

There is paucity of Brucella prevalence data in Malawi. For this reason, a cross-sectional study was conducted, from 06 January 2020 to 27 February 2020, to estimate the seroprevalence of brucellosis in dairy cattle herds amongst smallholder farmers, government and private dairy farms in the southern region. A total of 529 serum samples were screened for anti-Brucella antibodies using the Rose Bengal test (RBT) and a competitive enzyme-linked immunosorbent assay (cELISA). A pre-tested electronic (Epicollect tool, Wellcome Sanger Institute, United Kingdom) questionnaire was administered to 378 smallholder farmers to assess their knowledge, attitudes and practices towards brucellosis. Descriptive statistics were used to analyse the data in Microsoft Excel® and Statistical Package for Social Sciences (SPSS®) version 21. No animal tested positive for presence of anti-Brucella antibodies, indicating 0% prevalence (individual and herd levels). The majority (94.2%; 95% confidence interval [CI]: 91.8-96.5) of smallholder farmers had never heard about brucellosis. Furthermore, assisting during parturition without protective equipment (41.3%; 95% CI: 36.3-46.2) and using bulls for breeding (75%; 95% CI: 70.2-78.9) were amongst the common risk practices that were identified. We could not detect brucellosis in this study that indicates the disease could be very rare or even absent in the dairy cattle herds of the southern region of Malawi. However, further Brucella studies need to be conducted in cattle, small livestock, wildlife and humans to document the true status of brucellosis in the country. Brucellosis surveillance, monitoring, awareness and preventive measures are required to maintain this favourable situation.


Assuntos
Brucelose Bovina/epidemiologia , Brucelose Bovina/psicologia , Fazendeiros/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Criação de Animais Domésticos , Animais , Anticorpos Antibacterianos/sangue , Brucella/imunologia , Brucelose Bovina/sangue , Bovinos , Estudos Transversais , Indústria de Laticínios , Feminino , Humanos , Malaui/epidemiologia , Fatores de Risco , Estudos Soroepidemiológicos , Inquéritos e Questionários
11.
Artigo em Russo | MEDLINE | ID: mdl-34486871

RESUMO

The serologic epidemiological analysis of intensity of anti-diphtheria and anti-tetanus post-vaccination population immunity in the Republic of Kyrgyzstan was carried out. The presence of immune defense was determined in 453 residents by detecting IgG to diphtheria and tetanus by enzyme-linked immunosorbent assay using test system RIDASCREEN Diphtherie IgG and RIDASCREEN Tetanus IgG (Germany, R-Biopharm). It was established that the level of antibodies depends on the age of individuals. The highest immune defense against diphtheria is present in adult population aged 20-29 years (100%) and 30 years and older (100%). The lowest level is detected in the group of children of 1-4 years old and is up to 30.6%. The proportion of individuals with protective titer of antibodies ≥ 0.10 for diphtheria was 88.5%. The population intensity of post-vaccination tetanus immunity high antibody titers were established in age groups of 15-19 years (92.9%), 20-29 years (93.3%) and 30 years and older (94.8%). There is relationship between level of antibody titers and the age. Thus, in children age group of 5-9 years, high level of protection was established, that amounted up to 60.4%, in adolescents of 10-14 years old this indicator was 40%, and the lowest level in children aged of 1-4 years old was 39.6%.


Assuntos
Difteria , Tétano , Adolescente , Adulto , Anticorpos Antibacterianos , Criança , Pré-Escolar , Difteria/epidemiologia , Difteria/prevenção & controle , Humanos , Lactente , Quirguistão/epidemiologia , Tétano/prevenção & controle , Vacinação , Adulto Jovem
12.
Int J Infect Dis ; 111: 21-27, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34407478

RESUMO

OBJECTIVES: Pertussis is a respiratory infectious disease caused by Bordetella pertussis. In the Caribbean Netherlands (CN), comprising the islands Bonaire, St Eustatius, and Saba, registration of cases is mandatory for disease surveillance. However, insufficient laboratory facilities hamper case confirmation, and circulation persists. The aim of this seroepidemiological study was to gain insight into B. pertussis circulation in CN, and to investigate what factors contribute to the risk of infection. METHODS: Blood samples and questionnaires were collected for 1829 participants aged 0-90 years. Concentrations of B. pertussis toxin-specific IgG antibodies (anti-Pt) were determined using a bead-based immunoassay to indicate infections within the previous 12 months (based on anti-Pt ≥ 50 IU/mL) in participants without detectable vaccine-induced humoral immunity. Risk factors for recent infection were analyzed using logistic regression models. RESULTS: An estimated 8.2% (95% CI 6.6-10.1) of CN residents aged ≥ 9 years were found to have been recently infected by B. pertussis. Risk factors for a recent infection were age 12-29 years (13.8-14.6%) and Dutch Caribbean or Surinamese origin (10.7%). CONCLUSIONS: B. pertussis infections occur frequently among CN residents aged ≥ 9 years, although few clinical pertussis cases are reported. Transmission to vulnerable individuals seems likely and should be taken into account in optimizing vaccination programs.


Assuntos
Anticorpos Antibacterianos , Bordetella pertussis , Adolescente , Adulto , Países Baixos Caribenhos , Criança , Humanos , Vacina contra Coqueluche , Estudos Soroepidemiológicos , Adulto Jovem
13.
Vaccine ; 39(39): 5548-5556, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34419306

RESUMO

INTRODUCTION: Enterotoxigenic Escherichia coli (ETEC) is a common cause of infectious diarrhoea and a leading cause of morbidity and mortality in children living in resource-limited settings. It is also the leading cause of travellers' diarrhoea among civilian and military travellers. Its dual importance in global public health and travel medicine highlights the need for an effective vaccine. ETEC express colonization factors (CFs) that mediate adherence to the small intestine. An epidemiologically prevalent CF is coli surface antigen 6 (CS6). We assessed the safety and immunogenicity of a CS6-targeted candidate vaccine, CssBA, co-administered intramuscularly with the double-mutant heat-labile enterotoxin, dmLT [LT(R192G/L211A)]. METHODS: This was an open-label trial. Fifty subjects received three intramuscular injections (Days 1, 22 and 43) of CssBA alone (5 µg), dmLT alone (0.1 µg) or CssBA (5, 15, 45 µg) + dmLT (0.1 and 0.5 µg). Subjects were actively monitored for adverse events for 28 days following the third vaccination. Antibody responses (IgG and IgA) were characterized in the serum and from lymphocyte supernatants (ALS) to CS6 and the native ETEC heat labile enterotoxin, LT. RESULTS: Across all dose cohorts, the vaccine was safe and well-tolerated with no vaccine-related severe or serious adverse events. Among vaccine-related adverse events, a majority (98%) were mild with 79% being short-lived vaccine site reactions. Robust antibody responses were induced in a dose-dependent manner with a clear dmLT adjuvant effect. Response rates in subjects receiving 45 µg CssBA and 0.5 µg dmLT ranged from 50 to 100% across assays. CONCLUSION: This is the first study to demonstrate the safety and immunogenicity of CssBA and/or dmLT administered intramuscularly. Co-administration of the two components induced robust immune responses to CS6 and LT, paving the way for future studies to evaluate the efficacy of this vaccine target and development of a multivalent, subunit ETEC vaccine.


Assuntos
Toxinas Bacterianas , Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Vacinas contra Escherichia coli , Anticorpos Antibacterianos , Criança , Enterotoxinas , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/genética , Vacinas contra Escherichia coli/efeitos adversos , Temperatura Alta , Humanos , Vacinas de Subunidades
14.
Tidsskr Nor Laegeforen ; 141(11)2021 08 17.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-34423953

RESUMO

BACKGROUND: The diagnosis of pulmonary tularaemia can be challenging. We present a case illustrating how pulmonary tularaemia may be an important radiological differential diagnosis to lung cancer. CASE PRESENTATION: A man in his fifties presented with several weeks of dry cough, weight loss and profuse night sweats. The physical examination was normal. A chest computer tomography showed evidence of lymphadenopathy and two consolidated lung masses. The lung masses and lymph nodes showed signs of necrosis. The radiological findings were described as suspicious of lung cancer. A detailed history revealed that he had chopped wood prior to symptom onset. He tested positive for Francisella tularensis IgM and IgG, confirming the diagnosis of pulmonary tularaemia. INTERPRETATION: The radiological findings in pulmonary tularaemia may mimic lung cancer. Serology is an easy way to confirm the diagnosis, if faced with clinical or radiological suspicion of pulmonary tularaemia.


Assuntos
Francisella tularensis , Neoplasias Pulmonares , Tularemia , Anticorpos Antibacterianos , Tosse , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Tularemia/complicações , Tularemia/diagnóstico , Tularemia/tratamento farmacológico
15.
Ann Clin Lab Sci ; 51(4): 540-545, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452893

RESUMO

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae), an extracellular pathogen lacking a cell wall, causes respiratory infection in adults and children and has been implicated in asthma exacerbation; immunoglobulin (Ig) E may be involved in these exacerbations. Specific IgM and IgG immune response to M. pneumoniae has been reported, but less is known about IgE M. pneumoniae antibody (Ab) responses in asthma. Previous studies in our laboratory demonstrated that asthmatic children have increased IgM M. pneumoniae levels, but not IgE. Thus, we sought to investigate whether past M. pneumoniae infection triggers production of M. pneumoniae-specific IgE Abs in adult subjects with/without asthma. METHODS: M. pneumoniae- IgE and -IgM Ab responses were studied in adult asthmatic (N=22) and non-asthmatic (N=22) subjects (ELISA). Data are reported as antibody index. Threshold detection levels: IgE, IgM: 0.2, 0.9, respectively. RESULTS: M. pneumoniae-IgE Ab levels were low and below the threshold of detection in both asthmatic and non-asthmatics (0.002±0.008 vs. 0.02±0.03; P=0.021). However, specific-IgM levels were slightly higher in non-asthmatics compared with asthmatics (0.96±0.37 vs. 0.79±0.31; P=0.054). M. pneumoniae-IgM Ab positivity was similar in both groups (P=1.0). CONCLUSION: IgM M. pneumoniae Abs may play an important role in non-asthma and persist for months after acute infection. IgE M. pneumoniae Abs may play a less important role in both groups.


Assuntos
Anticorpos Antibacterianos/sangue , Asma/imunologia , Imunoglobulina E/imunologia , Imunoglobulina M/sangue , Mycoplasma pneumoniae/imunologia , Pneumonia por Mycoplasma/imunologia , Adulto , Anticorpos Antibacterianos/imunologia , Asma/sangue , Asma/complicações , Asma/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/etiologia , Prognóstico
16.
J Pharm Biomed Anal ; 205: 114302, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34388671

RESUMO

Physicochemical technologies are a powerful tool for the structural characterization of vaccine antigens both at bulk level as well as on the final formulation. High-field Nuclear Magnetic Resonance (NMR) spectroscopy has been found to be an extremely and robust tool for tracking the industrial process manufacturing of carbohydrate-based vaccines. I have applied NMR spectroscopy to the characterization of a penta-valent conjugate vaccine against Neisseria meninigitidis group A, C, W, Y (MenACWY) and Haemophilus influenzae type b (Hib) infections, constituted of capsule derived polysaccharide fragments independently conjugated to CRM197 protein carrier (CRM-MenA, CRM-MenC, CRM-MenW, CRM-MenY, CRM-Hib). 1H NMR has been used for the identity testing of the carbohydrate antigens and of the vaccine formulation. The application of NMR-based assays on multivalent conjugate vaccines looks to be a promising approach for identity and stability analyses useful for future vaccines development.


Assuntos
Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo C , Neisseria meningitidis , Anticorpos Antibacterianos , Haemophilus influenzae , Espectroscopia de Ressonância Magnética , Vacinas Conjugadas
17.
J Immunol ; 207(4): 1138-1149, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34341168

RESUMO

Group A streptococcal infections are a significant cause of global morbidity and mortality. A leading vaccine candidate is the surface M protein, a major virulence determinant and protective Ag. One obstacle to the development of M protein-based vaccines is the >200 different M types defined by the N-terminal sequences that contain protective epitopes. Despite sequence variability, M proteins share coiled-coil structural motifs that bind host proteins required for virulence. In this study, we exploit this potential Achilles heel of conserved structure to predict cross-reactive M peptides that could serve as broadly protective vaccine Ags. Combining sequences with structural predictions, six heterologous M peptides in a sequence-related cluster were predicted to elicit cross-reactive Abs with the remaining five nonvaccine M types in the cluster. The six-valent vaccine elicited Abs in rabbits that reacted with all 11 M peptides in the cluster and functional opsonic Abs against vaccine and nonvaccine M types in the cluster. We next immunized mice with four sequence-unrelated M peptides predicted to contain different coiled-coil propensities and tested the antisera for cross-reactivity against 41 heterologous M peptides. Based on these results, we developed an improved algorithm to select cross-reactive peptide pairs using additional parameters of coiled-coil length and propensity. The revised algorithm accurately predicted cross-reactive Ab binding, improving the Matthews correlation coefficient from 0.42 to 0.74. These results form the basis for selecting the minimum number of N-terminal M peptides to include in potentially broadly efficacious multivalent vaccines that could impact the overall global burden of group A streptococcal diseases.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Transporte/imunologia , Reações Cruzadas/imunologia , Vacinas Estreptocócicas/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Epitopos/imunologia , Feminino , Humanos , Masculino , Camundongos , Peptídeos/imunologia , Vacinas Sintéticas/imunologia
18.
Biomed Environ Sci ; 34(7): 528-539, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34353416

RESUMO

Objectives: To evaluate the immunogenicity of Mycobacterium intracellulare proteins and determine the cross-reactive proteins between M. intracellulare and M. tuberculosis. Methods: Protein extracts from M. intracellulare were used to immunize BALB/c mice. The antigens were evaluated using cellular and humoral immunoassays. The common genes between M. intracellular and M. tuberculosis were identified using genome-wide comparative analysis, and cross-reactive proteins were screened using immunoproteome microarrays. Results: Immunization with M. intracellulare proteins induced significantly higher levels of the cytokines interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-12 (IL-12), interleukin-6 (IL-6) and immunoglobulins IgG, IgG1, IgM, and IgG2a in mouse serum. Bone marrow-derived macrophages isolated from mice immunized with M. intracellulare antigens displayed significantly lower bacillary loads than those isolated from mice immunized with adjuvants. Whole-genome sequence analysis revealed 396 common genes between M. intracellulare and M. tuberculosis. Microchip hybridization with M. tuberculosis proteins revealed the presence of 478 proteins in the serum of mice immunized with M. intracellulare protein extracts. Sixty common antigens were found using both microchip and genomic comparative analyses. Conclusion: This is the advanced study to investigate the immunogenicity of M. intracellulare proteins and the cross-reactive proteins between M. intracellulare and M. tuberculosis. The results revealed the presence of a number of cross-reactive proteins between M. intracellulare and M. tuberculosis. Therefore, this study provides a new way of identifying immunogenic proteins for use in tuberculosis vaccines against both M. intracellulare and M. tuberculosis in future.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Complexo Mycobacterium avium/imunologia , Mycobacterium tuberculosis/imunologia , Animais , Reações Cruzadas , Citocinas/imunologia , Feminino , Genoma Bacteriano , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Macrófagos/imunologia , Camundongos Endogâmicos BALB C , Complexo Mycobacterium avium/genética , Mycobacterium tuberculosis/genética , Vacinas contra a Tuberculose/administração & dosagem , Sequenciamento Completo do Genoma
19.
Vaccine ; 39(36): 5095-5105, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34340858

RESUMO

BACKGROUND: Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule are the basis of vaccine-mediated protection. We examined the relationship between the dose of polysaccharide in pneumococcal conjugate vaccines (PCVs) and immunogenicity. METHODS: A systematic search of English publications that evaluated the immunogenicity of varying doses of pneumococcal conjugate vaccines was performed in Medline and Embase (Ovid Sp) databases in August 2019. We included only articles that involved administration of pneumococcal conjugate vaccine in humans and assessed the immunogenicity of more than one serotype-specific saccharide dose. Results were synthesised descriptively due to the heterogeneity of product valency, product content and vaccine schedule. RESULTS: We identified 1691 articles after de-duplication; 9 studies met our inclusion criteria; 2 in adults, 6 in children and 1 in both. Doses of polysaccharide evaluated ranged from 0.44 mcg to 17.6 mcg. In infants, all doses tested elicited IgG geometric mean concentrations (GMCs) above the established correlate of protection (COP; 0.35 mcg/ml). A month after completion of the administered vaccine schedule, 95% confidence intervals of only three out of all the doses evaluated had GMCs that crossed below the COP. In the adult studies, all adults achieved GMCs that would be considered protective in children who have received 3 standard vaccine doses. CONCLUSION: For some products, the mean antibody concentrations induced against some pneumococcal serotypes increased with increasing doses of the polysaccharide conjugate, but for other serotypes, there were no clear dose-response relationships or the dose response curves were negative. Fractional doses of polysaccharide which contain less than is included in currently distributed formulations may be useful in the development of higher valency vaccines, or dose-sparing delivery for paediatric use.


Assuntos
Infecções Pneumocócicas , Adulto , Anticorpos Antibacterianos , Criança , Pré-Escolar , Humanos , Lactente , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Streptococcus pneumoniae , Vacinas Conjugadas
20.
Vaccine ; 39(36): 5146-5152, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34340860

RESUMO

BACKGROUND: Parvovirus B19 (B19) is a well-known cause of fifth disease in children, but infection during pregnancy may cause hydrops fetalis and stillbirth. The receptor-binding domain (RBD) of the VP1 unique capsid plays a pivotal role in infection. Here, we aimed to improve the immunogenicity of an RBD-based vaccine by genetically fusing it with Streptococcus pneumoniae surface protein A (PspA). METHODS: Mice were intramuscularly injected with RBD-based vaccines. Antigen-specific antibodies and neutralizing activity against B19 were measured. Protective immunity against S. pneumoniae was evaluated by monitoring the survival of mice nasally challenged with bacteria and determining antigen-specific T cell activation in splenic cells. RESULTS: RBD alone failed to generate neutralizing antibodies against B19, but fusion with PspA induced higher levels of neutralizing IgG compared to B19 virus-like particles. Furthermore, a comparable level of PspA-specific IgG was induced by RBD-PspA and PspA alone, which was sufficient to protect mice against pneumococcal infection. Stimulation with PspA, but not RBD, induced cytokine production in splenic cells from mice immunized with RBD-PspA, suggesting that PspA-specific T cells supported immunoglobulin class switching of both RBD- and PspA-specific B cells. CONCLUSIONS: RBD-PspA should be an effective bivalent vaccine against B19 and S. pneumoniae infections.


Assuntos
Parvovirus B19 Humano , Infecções Pneumocócicas , Animais , Anticorpos Antibacterianos , Proteínas de Bactérias/genética , Camundongos , Camundongos Endogâmicos BALB C , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Receptores Virais , Streptococcus pneumoniae
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