RESUMO
Two plasmid gene protein (Pgp3)-based serological assays, the Pgp3-ELISA and multiplex bead assay (Pgp3-MBA), were compared and used to estimate seropositivity of Chlamydia trachomatis (CT) among females 14 to 39 years old participating in the National Health and Nutrition Examination Survey between 2013-2016. Of the 2,201 specimens tested, 502 (29.5%, 95% CI 27.6-31.5) were positive using Pgp3-ELISA and 624 (28.4%, 95% CI 26.5-30.3) were positive using Pgp3-MBA. The overall agreement between the assays was 87.7%. Corresponding nucleic acid amplification test (NAAT) results were available for 1,725 specimens (from women 18-39 years old); of these, 42 (2.4%, 95% CI 1.8-3.3) were CT NAAT-positive. Most of the CT NAAT-positive specimens had corresponding positive serological assay results; 33 (78.6%, 95% CI 62.8-89.2) were Pgp3-ELISA-positive and 36 (85.7%, 95% CI 70.8-94.1) were Pgp3-MBA-positive. Although Pgp3-ELISA and Pgp3-MBA demonstrated equivalent performance in this study, an advantage of the Pgp3-MBA over Pgp3-ELISA is that it is well suited for high sample throughput applications.
Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/imunologia , Adolescente , Adulto , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas de Amplificação de Ácido Nucleico , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Cholera remains a significant public health burden worldwide, and better methods for monitoring cholera incidence would enhance the effectiveness of public health interventions. The serum bactericidal assay (SBA) has been used extensively for Vibrio cholerae vaccine assessments and serosurveillance. Current SBA approaches for V. cholerae rely on colony enumeration or optical density (OD600nm) readings to measure viable bacteria following complement-mediated lysis. These methods provide titer values that are constrained to discrete dilution values and rely on bacterial outgrowth, which is time consuming and prone to variation. Detection of bacterial proteins following complement-mediated lysis presents a faster and potentially less variable alternative approach independent of bacterial outgrowth. Here, we present an SBA that measures luciferase luminescence driven by lysis-released adenylate kinase. This approach is faster and less variable than growth-dependent SBAs and directly measures continuous titer values. This novel SBA method can potentially be applied to other bacteria of interest.
Assuntos
Anticorpos Antibacterianos/imunologia , Cólera/epidemiologia , Ensaios de Anticorpos Bactericidas Séricos/métodos , Vibrio cholerae/imunologia , Cólera/imunologia , Cólera/prevenção & controle , Vacinas contra Cólera/uso terapêutico , Análise Custo-Benefício , Monitoramento Epidemiológico , Humanos , Imunogenicidade da Vacina , Medições Luminescentes , Reprodutibilidade dos Testes , Estudos Soroepidemiológicos , Fatores de TempoRESUMO
Cholera, a life-threatening disease caused by the Gram-negative bacterium Vibrio cholera, remains a concern in developing countries. The present study investigated the immunogenicity and protective immunity of outer membrane vesicles (OMVs) and combination of OMV and killed whole cells (WC) of a local strain isolated from the last outbreak in Iran in addition to reference and local strains of V. cholerae El Tor O1 in comparison to Dukoral vaccine in mice model. The protein content, morphology, and size of extracted OMVs were evaluated by electrophoresis and microscopic analyses, respectively. The serum titers of total immunoglobulin G (IgG), IgG1, IgG2a, and immunoglobulin A (IgA) in addition to secretory IgA and total IgG in different mice groups were determined by enzyme-linked immunosorbent assay (ELISA). In addition, fluid accumulation (FA) assay regarding the resistance to live strain of V. cholerae in ligated ileal loops was carried out to determine immunogenicity by OMV or combination of OMV and WC in comparison to that reported for Dukoral vaccine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified OMVs indicated protein profiles within the range of 34-52 kDa. Furthermore, transmission electron microscopy demonstrated the spherical shaped vesicles of 50-200 nm. The results of ELISA showed significant titers of systemic and mucosal immune anti-OMV IgGs in immunized BALB/c mice with different vaccine regimens. Additionally, a notable increase in the FA ratio was demonstrated in this study. The obtained results of the present study revealed that the WC-OMV combination of local strain can induce a high level of antibody response indicating more protection than OMV or WC separately. Moreover, it can be considered an effective immunogen against V. cholerae.
Assuntos
Vacinas contra Cólera/imunologia , Imunidade Humoral , Imunidade nas Mucosas , Vibrio cholerae/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Membrana Externa Bacteriana/imunologia , Feminino , Imunogenicidade da Vacina , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The Yersinia pestis capsular antigen F1 is widely used in plague laboratory diagnosis. Here, we describe the production of an F1 recombinant protein within reduced time and biosafety requirements. Its evaluation in hemagglutination tests indicated that the recombinant F1 can replace the conventional F1 protein for plague diagnosis.
Assuntos
Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Custos e Análise de Custo , Peste/diagnóstico , Peste/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Modelos Animais de Doenças , Testes de Hemaglutinação/métodos , Masculino , Coelhos , Proteínas Recombinantes/imunologia , Fatores de TempoRESUMO
F4 (K88) and F18 fimbriaed enterotoxigenic Escherichia coli (ETEC) are the predominant causes of porcine postweaning diarrhea (PWD), and vaccines are considered the most effective preventive approach against PWD. Since heterologous DNA integrated into bacterial chromosomes could be effectively expressed with stable inheritance, we chose probiotic EcNc (E. coli Nissle 1917 prototype cured of cryptic plasmids) as a delivery vector to express the heterologous F4 or both F4 and F18 fimbriae and sequentially assessed their immune efficacy of anti-F4 and F18 fimbriae in both murine and piglet models. Employing the CRISPR-cas9 technology, yjcS, pcadA, lacZ, yieN/trkD, maeB, and nth/tppB sites in the chromosome of an EcNc strain were targeted as integration sites to integrate F4 or F18 fimbriae cluster genes under the Ptet promotor to construct two recombinant integration probiotic strains (RIPSs), i.e., nth integration strain (EcNcΔnth/tppB::PtetF4) and multiple integration strain (EcNc::PtetF18x4::PtetF4x2). Expression of F4, both F4 and F18 fimbriae on the surfaces of two RIPSs, was verified with combined methods of agglutination assay, Western blot, and immunofluorescence microscopy. The recombinant strains have improved adherence to porcine intestinal epithelial cell lines. Mice and piglets immunized with the nth integration strain and multiple integration strain through gavage developed anti-F4 and both anti-F4 and anti-F18 IgG immune responses. Moreover, the serum antibodies from the immunized mice and piglets significantly inhibited the adherence of F4+ or both F4+ and F18+ ETEC wild-type strains to porcine intestinal cell lines in vitro, indicating the potential of RIPSs as promising probiotic strains plus vaccine candidates against F4+/F18+ ETEC infection.
Assuntos
Sistemas CRISPR-Cas/genética , Cromossomos Bacterianos , Escherichia coli Enterotoxigênica/genética , Adesinas de Escherichia coli/imunologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Aderência Bacteriana , Linhagem Celular , Escherichia coli Enterotoxigênica/imunologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/imunologia , Feminino , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Família Multigênica , SuínosRESUMO
Vaccines typically contain an antigen, delivery system (vehicle), and adjuvant, all of which contribute to inducing a potent immune response. Consequently, design of new vaccines is difficult, because the contributions and interactions of these components are difficult to distinguish. Here, it is aimed to develop an easy-to-use, non-immunogenic, injectable depot system for sustained antigen release that will be suitable for assessing the efficacy of prolonged antigen exposure per se for inducing an immune response. This should mimic real-life infections. Recombinant elastin-like polypeptides with periodic cysteine residues (cELPs) are selected, which reportedly show little or no immunogenicity, as carriers and tetanus toxoid (Ttd) as an antigen. After subcutaneous injection of the mixture, cELP rapidly forms a disulfide cross-linked hydrogel in situ, within which Ttd is physically incorporated, affording a biodegradable antigen depot. A series of Ttd-containing hydrogels is examined. A single injection induces high levels of tetanus antibody with high avidity for at least 20 weeks in mice. The chain length of cELP proves critical, whereas differences in hydrophobicity has little effect, although hydrophilic cELPs are more rapidly biodegraded. This system's ability to distinguish the contribution of sustained antigen release to antibody induction should be helpful for rational design of next-generation vaccines.
Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos , Elastina , Hidrogéis , Imunogenicidade da Vacina , Toxoide Tetânico , Animais , Antígenos/química , Antígenos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Elastina/química , Elastina/farmacologia , Feminino , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Toxoide Tetânico/química , Toxoide Tetânico/farmacologiaRESUMO
Pertussis is a human respiratory infection caused by the gram-negative bacterium, Bordetella pertussis. To evaluate the pertussis burden and vaccine efficacy, diagnosis and epidemiological surveillance should be based on accurate and valid diagnostic methods. Recently, the serodiagnostic tests Novagnost Bordetella pertussis IgA and IgM were approved in Japan for pertussis diagnostics. Although the anti-pertussis toxin (PT) IgG assay has been used for pertussis diagnosis worldwide, little is known about the anti-B. pertussis IgA and IgM assays. In this study, serum samples from 460 healthy donors were examined to determine the seroprevalence of anti-B. pertussis IgA and IgM in a Japanese population, and its correlation with donor age. Our data demonstrated that anti-B. pertussis IgA and IgM are positively and negatively correlated with age (r = 0.27, r = -0.37; P < 0.001, respectively). Age-specific analysis revealed high titers of anti-B. pertussis IgA in adults (46-50 years), while anti-B. pertussis IgM titers were high in schoolchildren (6-10, 11-15 years). When applying the arbitrary cut-off values for these ages, 17.6% and 39.5% of healthy donors were interpreted as pertussis-positive or indeterminate with anti-B. pertussis IgA (46-50 years) and IgM (11-15 years) titers, respectively. Overall, our findings indicated that the Novagnost Bordetella pertussis IgA and IgM testing could be greatly affected by subject age, limiting its value for pertussis diagnosis.
Assuntos
Anticorpos Antibacterianos/sangue , Bordetella pertussis/imunologia , Imunoglobulina A/sangue , Imunoglobulina M/sangue , Coqueluche/epidemiologia , Adolescente , Adulto , Anticorpos Antibacterianos/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Lactente , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Coqueluche/sangue , Coqueluche/microbiologia , Adulto JovemRESUMO
Mycobacterium tuberculosis (M. tuberculosis) persistent infection might cause the dysfunction of hematopoiesis. To investigate whether M. tuberculosis persistent antigen stimulation impairs the proliferation and differentiation of hematopoietic stem and progenitor cells characterized as lineage- c-Kit+ (LK cells), C57BL/6 mice were primed with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and boosted with a cocktail of M. tuberculosis antigens ESAT6, CFP10 and Mtb10.4-HspX (MH) along with adjuvant N, N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA) plus polyinosinic-polycytidylic acid (Poly I:C) weekly for 12 or 22 weeks. The cytokine production by splenic T cells, proliferation of LK cells and transcriptional events during differentiation of bone marrow (BM) c-Kit+ cells were investigated. Meanwhile, the mice were treated with interleukin 2 (IL-2) and the therapeutic effects were analyzed. We found that antigen specific interferon-γ (IFN-γ) production by splenic CD4+ T cells increased following antigen stimulation for 12 weeks, but it declined after continuous stimulation for 22 weeks. The long-term exposure of mice to M. tuberculosis antigen compromised the proliferation of LK cells. Moreover, the expression of transcription factors in the c-Kit+ cells was adjusted, with up-regulation of IRF8 and Batf2 involved in myeloid differentiation and down-regulation of NOTCH1 and GATA2 participated in T-cell lineage commitment. The concentrations of IFN-γ in BM of the persistent antigen group were higher than that in sham control at the 12th week, while the concentrations of IL-2 in BM of the persistent antigen group were lower compared with the transient antigen stimulation control. Following IL-2 treatment, the concentrations of IL-2 in BM increased while IFN-γ got declined. IL-2 treatment could restore the expression levels of those transcription factors and the proliferating activity of LK cells impaired by persistent antigen stimulation. Our results indicate that M. tuberculosis antigen persistent stimulation decreases the proliferating activity of LK cells, promotes myelopoietic differentiation, and represses lymphopoietic differentiation as a consequence of elevated IFN-γ production. IL-2 supplementation contributes to maintaining the homeostasis of hemopoiesis.
Assuntos
Antígenos de Bactérias/imunologia , Medula Óssea/imunologia , Proliferação de Células/fisiologia , Mycobacterium tuberculosis/imunologia , Transcrição Gênica/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/imunologia , Medula Óssea/microbiologia , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Interferon gama/imunologia , Interleucina-2/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium bovis/imunologia , Fatores de Transcrição/imunologiaRESUMO
Brucellosis is caused by the genus Brucella. Brucella is widely distributed in cattle, swine, sheep, goat and other mammals including human. Animal brucellosis causes severe economic losses and affects related international transportation and trade. Human brucellosis causes both acute and chronic symptoms of multi-organ dysfunction. Brucella type IV secretion system (T4SS) VirB5 was required for macrophages infection and essential for virulence in mice. VirB5 is located on the cell surface and serves as a specific adhesin targeting host cell receptors. The aim of this study was to isolate and characterize a specific human domain antibody against Brucella abortus (B. abortus) VirB5 from human single domain antibody (sdAb or VHH) phage display library. Following five rounds of screening, an sdAb named as BaV5VH4 showed the highest affinity by enzyme-linked immunosorbent assay (ELISA). Its interaction with B. abortus VirB5 was verified by binding assay, dot blot and molecular docking. These findings in this paper could greatly help elucidate the molecular mechanisms of Brucella infection, and accelerate the development of sdAbs-based vaccines and neutralizing therapeutics of brucellosis.
Assuntos
Anticorpos Antibacterianos/imunologia , Brucella abortus/imunologia , Brucelose/prevenção & controle , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos/genética , Anticorpos Antibacterianos/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/isolamento & purificação , Bacteriófagos/imunologia , Sequência de Bases , Brucella abortus/genética , Brucella abortus/isolamento & purificação , Brucelose/economia , Bovinos , Ensaio de Imunoadsorção Enzimática , Cabras , Humanos , Immunoblotting , Camundongos , Simulação de Acoplamento Molecular , Filogenia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Ovinos , Suínos , Virulência , Fatores de Virulência/metabolismo , Zoonoses/prevenção & controleRESUMO
Helicobacter pylori (H. pylori) chronic infection causes severe digestive diseases, including gastric cancer, and certain strains entail a higher risk. Risk factors for this infection are still not fully understood. The aim of this study was to describe the association of adult and childhood sociodemographic factors with the seroprevalence of H. pylori, and with CagA and VacA antigen-specific seropositivity among H. pylori-seropositive individuals in the Spanish adult population. Serum antibody reactivity to H. pylori proteins was evaluated using multiplex serology in 2555 population-based controls enrolled in the MCC-Spain study, a multicase-control study recruiting participants from 2008 to 2013 in different areas of Spain. H. pylori seroprevalence was defined as seropositivity against at least four bacterial proteins. Information on sociodemographics, lifestyles, and environmental exposures was collected through personal interviews. Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models to assess the association of lifetime sociodemographic factors with H. pylori seroprevalence and with seropositivity for CagA and VacA. H. pylori seroprevalence was 87.2%. Seropositivity was statistically significantly higher in men, increased with age, BMI, and number of siblings, and decreased with education and socioeconomic family level at birth. Among H. pylori-seropositive individuals, seropositivity was 53.3% for CagA, 61.4% for VacA, and 38.8% for both CagA and VacA. Ever smokers had lower seroprevalence for CagA and VacA than never smokers. H. pylori seroprevalence among this Spanish adult population was high and one third of the population was seropositive for two well-known markers of gastric cancer risk: CagA and VacA. Sex, age, education, and BMI were associated with H. pylori seroprevalence.
Assuntos
Anticorpos Antibacterianos/sangue , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Fatores Socioeconômicos , Neoplasias Gástricas/prevenção & controle , Fatores Etários , Idoso , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Estudos Transversais , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Sexuais , Espanha/epidemiologia , Neoplasias Gástricas/microbiologia , Fatores de TempoRESUMO
Bacterial coldwater disease, caused by Flavobacterium psychrophilum, remains one of the most significant bacterial diseases of salmonids worldwide. A previously developed and reported live-attenuated immersion vaccine (F. psychrophilum; B.17-ILM) has been shown to confer significant protection to salmonids. To further characterize this vaccine, a series of experiments were carried out to determine the cross-protective efficacy of this B.17-ILM vaccine against 9 F. psychrophilum isolates (representing seven sequence types/three clonal complexes as determined by multilocus sequence typing) in comparison with a wild-type virulent strain, CSF-259-93. To assess protection, 28-day experimental challenges of rainbow trout (Oncorhynchus mykiss) fry were conducted following immersion vaccinations with the B.17-ILM vaccine. F. psychrophilum strains used in challenge trials were isolated from several fish species across the globe; however, all were found to be virulent in rainbow trout. The B.17-ILM vaccine provided significant protection against all strains, with relative percent survival values ranging from 51% to 72%. All vaccinated fish developed an adaptive immune response (as measured by F. psychrophilum-specific antibodies) that increased out to the time of challenge (8 weeks postimmunization). Previous studies have confirmed that antibody plays an important role in protection against F. psychrophilum challenge; therefore, specific antibodies to the B.17-ILM vaccine strain appear to contribute to the cross-protection observed to heterologous strain. The ability of such antibodies to bind to similar antigenic regions for all strains was confirmed by western blot analyses. Results presented here support the practical application of this live-attenuated vaccine, and suggest that it will be efficacious even in aquaculture operations affected by diverse strains of F. psychrophilum.
Assuntos
Vacinas Bacterianas/imunologia , Proteção Cruzada , Doenças dos Peixes/prevenção & controle , Infecções por Flavobacteriaceae/veterinária , Vacinas Atenuadas/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/administração & dosagem , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Infecções por Flavobacteriaceae/imunologia , Infecções por Flavobacteriaceae/microbiologia , Infecções por Flavobacteriaceae/prevenção & controle , Flavobacterium/classificação , Oncorhynchus mykiss/imunologia , Vacinas Atenuadas/administração & dosagemRESUMO
PURPOSE: Nontypeable Haemophilus influenzae (NTHi) is a commensal in the human nasopharynx and the cause of pneumonia, meningitis, sinusitis, acute exacerbations of chronic obstructive pulmonary disease and acute otitis media (AOM). AOM is the most common ailment for which antibiotics are prescribed in the United States. With the emergence of new strains of antibiotic-resistant bacteria, finding an effective and broad coverage vaccine to protect against AOM-causing pathogens has become a priority. Mouse models are a cost-effective and efficient way to help determine vaccine efficacy. Here, we describe an NTHi AOM model in C57BL/6J mice, which also utilizes a mouse-adapted H1N1 influenza virus to mimic human coinfection. METHODOLOGY: We tested our coinfection model using a protein vaccine formulation containing protein D, a well-studied NTHi vaccine candidate that can be found in the 10-valent Streptococcus pneumoniae conjugate vaccine. We verified the usefulness of our mouse model by comparing bacterial loads in the nose and ear between protein D-vaccinated and control mice. RESULTS: While there was no measurable difference in nasal bacterial loads, we did detect significant differences in the bacterial loads of ear washes and ear bullae between vaccinated and control mice. CONCLUSION: The results from this study suggest that our NTHi AOM coinfection model is useful for assessing protein vaccines.
Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Transporte/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae/imunologia , Imunoglobulina D/imunologia , Lipoproteínas/imunologia , Otite Média/prevenção & controle , Administração Intranasal , Animais , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/genética , Proteínas de Transporte/administração & dosagem , Proteínas de Transporte/genética , Coinfecção/microbiologia , Coinfecção/prevenção & controle , Coinfecção/virologia , Modelos Animais de Doenças , Feminino , Infecções por Haemophilus/microbiologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/genética , Haemophilus influenzae/genética , Haemophilus influenzae/crescimento & desenvolvimento , Humanos , Imunoglobulina D/administração & dosagem , Imunoglobulina D/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Lipoproteínas/administração & dosagem , Lipoproteínas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nariz/microbiologia , Nariz/virologia , Otite Média/imunologia , Otite Média/microbiologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologiaRESUMO
Response to polysaccharide vaccination can be an invaluable tool for assessing functionality of the adaptive immune system. Measurement of antibodies raised in response to Pneumovax®23 is the current gold standard test, but there are significant challenges and constraints in both the measurement and interpretation of the response. An alternative polysaccharide vaccine approach (Salmonella typhi Vi capsule (ViCPS)) has been suggested. In the present article, we review current evidence for the measurement of ViCPS antibodies in the diagnosis of primary and secondary antibody deficiencies. In particular, we review emerging data suggesting their interpretation in combination with the response to Pneumovax®23 and comment upon the utility of these vaccines to assess humoral immune responses while receiving immunoglobulin replacement therapy (IGRT).
Assuntos
Imunidade Adaptativa , Anticorpos Antibacterianos/sangue , Polissacarídeos Bacterianos/imunologia , Salmonella typhi/imunologia , Febre Tifoide/imunologia , Vacinas Tíficas-Paratíficas/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunização Passiva , Síndromes de Imunodeficiência , Camundongos , Vacinas Pneumocócicas/imunologia , Testes Sorológicos , Febre Tifoide/diagnósticoRESUMO
CONTEXT: Salivary antibodies may act as non-invasive marker of systemic immunity enabling assessment of vaccination and protection against bacterial infections. OBJECTIVE: To assess if levels of anti-pneumococcal (Pn) antibodies in saliva reflect concentrations in serum and determine whether saliva can accurately identify protective concentrations in serum. METHODS: IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 Pn polysaccharide antigens in 72 healthy adults. RESULTS: Antibody levels in saliva correlated positively with serum across immunoglobulin classes, most strongly for IgA. Individuals who had protective antibody levels in serum demonstrated significantly higher IgG and IgA salivary antibody concentrations/secretion rates. Salivary IgG and IgA Pn antibodies were able to distinguish between those with/without protective levels in serum for the majority of serotypes. Salivary IgM antibodies were not able to differentiate protective status. Median IgG and IgA Pn salivary parameters were able to identify individuals who had protective levels in serum on ≥8/12 serotypes with moderate accuracy: median IgA secretion rates provided the best sensitivity (73%) and specificity (71%). CONCLUSIONS: These findings suggest that IgG and IgA Pn specific antibodies in saliva may be useful surrogate markers of antibody status in serum.
Assuntos
Anticorpos Antibacterianos/imunologia , Biomarcadores/análise , Infecções Pneumocócicas/imunologia , Saliva/imunologia , Streptococcus pneumoniae/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Feminino , Humanos , Imunoglobulina A Secretora/sangue , Imunoglobulina A Secretora/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/sangue , Infecções Pneumocócicas/microbiologia , Saliva/microbiologia , Streptococcus pneumoniae/fisiologia , Adulto JovemAssuntos
Imunidade Humoral , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Vacinação , Anticorpos Antibacterianos/imunologia , Humanos , Imunogenicidade da Vacina , Infecções Pneumocócicas/prevenção & controle , Vacinação/métodosRESUMO
BACKGROUND: Our reverse syphilis testing algorithm consists of a treponemal IgG multiplex flow immunoassay (MFI) followed by both rapid plasma reagin titer and the Treponema pallidum particle agglutination (TPPA) test on specimens with a reactive MFI result. We report here the impact of a modified reverse algorithm, in which the strength of signal of the MFI is used to avoid unnecessary TPPA testing. METHODS: The Bioplex syphilis IgG MFI was used as the syphilis screening assay, and specimens with equivocal (antibody index 0.9 or 1.0), or reactive (antibody index ≥ 1.1) results were further tested by rapid plasma reagin titer and TPPA test. We performed a retrospective, descriptive analysis of all specimens received for syphilis screening between January and May of 2014. A cost analysis was performed, taking into account labor and reagent expenses. RESULTS: In our diverse patient population consisting of high-risk incarcerated persons, low-risk obstetrical/gynecological patients and high-risk miscellaneous clinic and inpatients, 430 (65%) of 665 MFI-positive specimens had antibody indices of 8 or greater. Greater than 99% of these specimens were reactive by the TPPA test. Avoiding TPPA testing of specimens with an MFI antibody index ≥8 would save over US $4800 annually in laboratory costs. CONCLUSIONS: The TPPA testing is unnecessary on specimens with MFI antibody indices ≥8. This would substantially reduce the TPPA testing volume and also reduce laboratory expenses.
Assuntos
Anticorpos Antibacterianos/imunologia , Sífilis/diagnóstico , Treponema pallidum/isolamento & purificação , Testes de Aglutinação , Algoritmos , Feminino , Humanos , Imunoensaio , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Sífilis/microbiologia , Sorodiagnóstico da Sífilis/economia , Treponema pallidum/imunologiaRESUMO
Lyme disease case misclassification, a top public health concern, may be attributed to the current disconnect between clinical diagnosis and surveillance. This study examines Lyme disease distribution in West Virginia (WV) and determines clinicians' knowledge of both disease and surveillance. Lyme disease surveillance data for 2013 were obtained from the WV Bureau for Public Health. A validated survey, distributed to clinicians at an academic medical center, assessed clinicians' knowledge of disease diagnosis and surveillance. There were 297 adult Lyme disease cases of which 83 were confirmed. Clinician survey responses resulted in a correct response rate of 70% for Lyme disease knowledge questions. Fewer than half of all clinicians were aware of the surveillance criteria for confirming Lyme disease cases. Neither medical specialty nor previous treatment of patients with Lyme disease were significantly associated with clinicians' knowledge of the disease. Clinicians in WV are familiar with symptoms and clinical management of Lyme disease. However, they are less knowledgeable about diagnosis and public health surveillance comprising reporting and confirming cases of the disease. Clinicians and public health authorities should collaborate more closely to promote education and awareness as a key step to successfully reducing the burden of Lymne disease.
Assuntos
Competência Clínica , Monitoramento Epidemiológico , Doença de Lyme/epidemiologia , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/imunologia , Medicina de Emergência , Medicina de Família e Comunidade , Humanos , Medicina Interna , Doença de Lyme/diagnóstico , Doença de Lyme/tratamento farmacológico , Saúde Pública , Inquéritos e Questionários , West Virginia/epidemiologiaRESUMO
Periodontitis is the most prevalent infectious disease and related to oral and systemic health, therefore novel prophylaxis to prevent the disease is highly desirable. Here, we assessed the outer membrane vesicles (OMVs) of a keystone periodontal pathogen, Porphyromonas gingivalis, as a candidate mucosal immunogen and adjuvant for a periodontitis vaccine. The structural and functional stability of OMVs, demonstrated by proteinase K resistance and ability to withstand long-term storage, are considered advantageous for carrying the OMV components into the host immune system. Intranasal vaccination of OMVs in mice elicited production of P. gingivalis-specific antibodies in blood and saliva by OMVs in a dose-dependent manner, which was dramatically enhanced by addition of a TLR3 agonist, Poly(I:C). Serum samples from mice immunized with OMVs plus Poly(I:C) adjuvant [OMV+Poly(I:C)] showed significant inhibition of gingipain proteolytic activity of not only the vaccine strain, but also heterologous strains. The viability of P. gingivalis was also decreased by preincubation with OMV+Poly(I:C)-immunized sera, while the killing effect was partially blocked by heat-inactivation of the sera. Saliva samples from mice immunized with OMV+Poly(I:C) enhanced bacterial agglutination of both the vaccine and heterologous strains. In an oral infection mouse model, the numbers of P. gingivalis in the oral cavity were significantly decreased in mice intranasally immunized with OMV+Poly(I:C) as compared to mock (only Poly[I:C])-immunized mice. The high levels of serum IgG (including IgG1 and IgG2a) and salivary S-IgA were elicited in mice intranasally immunized with OMV+Poly(I:C), which were maintained for at least 28 and 18weeks, respectively, after immunization. An experiment examining the accumulation of OMVs after intranasal immunization in proximal organs and an intracerebral injection experiment confirmed the safety of OMVs. Based on our results, we propose that intranasal immunization with OMV+Poly(I:C) is a feasible vaccine strategy in the context of bacterial clearance and safety.
Assuntos
Vacinas Bacterianas/imunologia , Micropartículas Derivadas de Células/imunologia , Imunidade nas Mucosas , Periodontite/prevenção & controle , Porphyromonas gingivalis/imunologia , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Mucosa/imunologia , Poli I-C , Polinucleotídeos/administração & dosagem , Saliva/imunologiaRESUMO
Pneumonia is the fourth-leading cause of death globally, and Streptococcus pneumoniae is the most important causative pathogen. Because the incidence of pneumococcal diseases is likely to increase with the aging society, we should determine an optimal strategy for pneumococcal vaccination. While consensus indicates that 23-valent pneumococcal polysaccharide vaccine prevents invasive pneumococcal diseases (IPD), its effects on community-acquired pneumonia (CAP) remain controversial. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was released. The latest clinical study (CAPiTA study) showed that PCV13 reduced vaccine-type CAP and IPD. Based on these results, the Advisory Committee on Immunization Practices recommended initial vaccination with PCV13 for the elderly. Scientific evidence regarding immunosenescence is needed to determine a more ideal vaccination strategy for the elderly with impaired innate and adaptive immunity. Continuing research on the cost effectiveness of new vaccine strategies considering constantly changing epidemiology is also warranted.
Assuntos
Infecções Comunitárias Adquiridas/prevenção & controle , Imunossenescência/imunologia , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas Conjugadas/imunologia , Comitês Consultivos , Envelhecimento , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Centers for Disease Control and Prevention, U.S. , Infecções Comunitárias Adquiridas/microbiologia , Análise Custo-Benefício , Humanos , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Estados Unidos , VacinaçãoRESUMO
BACKGROUND: We compared the immunogenicity, safety and 1-year antibody persistence of a single-dose and a 2-dose series of a licensed meningococcal ACWY-CRM conjugate vaccine (MenACWY-CRM) in 2- to 10-year-old children. METHODS: In this phase III, multicenter, observer-blind study, children aged 2-5 years (n = 359) and 6-10 years (n = 356) were randomized 1:1 to receive 2 doses of MenACWY-CRM (ACWY2) or 1 dose of placebo followed by 1 dose of MenACWY-CRM (ACWY1), 2 months apart. Immunogenicity was measured using serum bactericidal activity with human complement (hSBA). Primary outcomes were to assess the immunologic noninferiority and superiority of ACWY2 versus ACWY1. RESULTS: One-month after the second dose, the hSBA seroresponse in ACWY2 was noninferior to ACWY1 for all 4 serogroups, in both age cohorts, and was superior for serogroups C and Y in the 2- to 5-year-old age cohort and for serogroup Y in the 6- to 10-year-old age cohort. Overall, 90%-99% of subjects in ACWY2 and 65%-96% in ACWY1 had hSBA titers ≥ 8; geometric mean titers were 1.8- to 6.4-fold higher in ACWY2 than ACWY1 across serogroups. At 1 year postvaccination, geometric mean titers declined, and the differences between ACWY2 and ACWY1 remained significant for serogroups A and C in the 2- to 5-year-old age cohort and for serogroups C and Y in the 6- to 10-year-old age cohort. The safety profile of MenACWY-CRM was similar in both groups. CONCLUSIONS: The single dose and 2-dose MenACWY-CRM series were immunogenic and well tolerated. Although antibody responses were greater after 2 doses, especially in the 2- to 5-year-old age cohort, this difference was less pronounced at 1 year postvaccination.