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1.
Microb Pathog ; 160: 105184, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34508828

RESUMO

Hepatitis B virus (HBV) infection is limited through vaccination against HBsAg formulated in the Alum adjuvant. However, this alum-formulated vaccine fails to be preventive in some cases, also known as non-responders. Recent studies have shown the immunomodulatory effect of α-tocopherol in various models. Here, we developed a new formulation for HBsAg using α-tocopherol, followed by assessment of immune responses. Experimental BALB/c mice were immunized with a commercial alum-based vaccine or the one formulated in α-tocopherol at different doses. Mice were immunized subcutaneously with 5 µg of HBsAg with different formulations three times with 2-week intervals. Specific total IgG, IgG1, and IgG2a isotypes of antibodies were measured by ELISA. Immunologic cytokines, such as IFN-γ, IL-4, IL-2, and TNF-α, were also evaluated through commercial ELISA kits. Our results showed that the new α-tocopherol-formulated vaccine had the ability to reinforce specific total IgG responses. Moreover, α-tocopherol in the HBsAg vaccine increased IFN-γ, IL-2, and TNF-α cytokines at higher concentrations; however, the vaccine suppressed IL-4 cytokine release. At a lower concentration of α-tocopherol, the IL-4 cytokine response increased without a positive effect on IFN-γ and TNF-α cytokine response. It seems that α-tocopherol can change the immune responses against HBsAg; however, the type of response depends on the dose of α-tocopherol used in the vaccine formulation.


Assuntos
Citocinas , Vacinas contra Hepatite B , Interferon gama/imunologia , Adjuvantes Imunológicos , Animais , Citocinas/imunologia , Anticorpos Anti-Hepatite B , Vacinas contra Hepatite B/imunologia , Camundongos , Camundongos Endogâmicos BALB C
2.
PLoS One ; 16(7): e0246915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34297725

RESUMO

Although aluminum-containing adjuvants are widely used in human vaccination due to their excellent safety profile, they exhibit low effectiveness with many recombinant antigens. This study investigated the adjuvanticity of snail mucin with recombinant Hepatitis B Vaccine (rHBsAg). Twenty-five (25) female mice distributed unbiasedly into 5 groups were used in the study and were administered different rHBsAg/Mucin formulation at 7 days intervals. Blood samples were collected a day following the administration for analysis. The results of liver function and body weight analysis were indications that snail mucin had no adverse effect on the mice. The treatment group (administer mucin and rHBsAg) showed significantly (P<0.05) higher mean titres of anti-HBsAg antibodies when compared with the negative controls and the positive control administered with two doses of rHBsAg after the boost doses (day 28). Furthermore, a comparable immune response to positive control administered with three doses rHBaAG was recorded. In silico prediction, studies of the protein-protein interaction of a homology modelled snail mucus protein and HBsAg gave an indication of enhanced HBV antigen-antibody interaction. Therefore, this study has shown that snail mucin possesses some adjuvant properties and enhances immune response towards rHBsAg vaccine. However, there is a need for further molecular dynamics studies to understand its mechanism of action.


Assuntos
Vacinas contra Hepatite B/imunologia , Mucinas/imunologia , Caramujos/imunologia , Animais , Camundongos
3.
PLoS One ; 16(7): e0253752, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34197516

RESUMO

BACKGROUND: Despite completion of the vaccine schedule for hepatitis B virus (HBV), children may display levels of HBV surface antibodies (anti-HBs) that are considered inadequate for sufficient protection (<10 IU/L). AIMS: Our aim was to investigate if age and gap time between HBV vaccine doses may negatively affect the levels of anti-HBs in children, and if these relationships are modified by sex. METHODS: In a high-endemic HBV region of the western Brazilian Amazon we enrolled children who had completed the HBV vaccine schedule. All children underwent analysis of anti-HBs and a clinical examination. RESULTS: We included 522 children (mean age 4.3 ± 0.8 years; 50% male). Median anti-HBs was 28.4 [interquartile range (IQR) 5.4 to 128.6] IU/L and 32% had anti-HBs <10 IU/L. The median gap time from last to preceding dose was 2.4 [IQR 2.1 to 3.3] months. Levels of anti-HBs decreased with higher age (-42% per year increase [95%CI -56% to -24%], p<0.001), but not with longer gap time (+23% per month increase [95%CI -16% to +62%], p = 0.249). After adjusting for relevant confounders, gap time became significant (p = 0.032) and age remained a significant predictor of anti-HBs (p<0.001). CONCLUSION: One third of assessed children displayed anti-HBs <10 IU/L. Levels of anti-HBs decreased with higher age and increased with longer gap time between the last two doses.


Assuntos
Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Esquemas de Imunização , Fatores Etários , Brasil , Pré-Escolar , Estudos Transversais , Doenças Endêmicas/prevenção & controle , Feminino , Hepatite B/sangue , Hepatite B/prevenção & controle , Hepatite B/virologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Humanos , Masculino , Vacinação em Massa , Testes Sorológicos/estatística & dados numéricos , Fatores de Tempo
4.
BMC Infect Dis ; 21(1): 582, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134644

RESUMO

BACKGROUND: Refugees are frequently not immune to vaccine-preventable infections. Adherence to consensus guidelines on vaccination and infectious diseases screening among refugees resettling in the U.S. is unknown. We sought to determine rates of vaccine completion and infectious diseases screening in refugees following resettlement. METHODS: We conducted a retrospective cohort study of refugees resettling in a region in the U.S. using medical data from June 2013-April 2015. We determined the proportion of vaccine-eligible refugees vaccinated with measles-mumps-rubella (MMR), hepatitis A/B, tetanus, diphtheria, and acellular pertussis (Tdap), and human papillomavirus (HPV) following resettlement. We also determined the proportion of refugees who completed HIV and hepatitis C (HCV) screening. RESULTS: One hundred and eleven subjects were included, primarily from Iraq (53%), Afghanistan (19%), and Eritrea (11%). Of the 84 subjects who were vaccine-eligible, 78 (93%) initiated and 42 (50%) completed vaccinations within one year of resettlement. Odds of completing vaccination were higher for men (OR: 2.38; 95%CI:1.02-5.71) and for subjects with English proficiency (OR: 3.70; 95%CI:1.04-17.49). Of the 78 subjects (70%) completing HIV screening, two (3%) were diagnosed with HIV. Nearly all subjects completed screening for HCV, and one had active infection. CONCLUSION: While most refugees initiate vaccinations, only 50% completed vaccinations and 70% completed HIV screening within 1 year of resettlement. There is a need to emphasize vaccine completion and HIV screening in refugee patients following resettlement.


Assuntos
Doenças Transmissíveis/diagnóstico , Refugiados/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Doenças Transmissíveis/imunologia , Feminino , Infecções por HIV/diagnóstico , Vacinas contra Hepatite B/imunologia , Humanos , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Pessoa de Meia-Idade , Razão de Chances , Vacinas contra Papillomavirus/imunologia , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
5.
Lancet Infect Dis ; 21(9): 1271-1281, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33989539

RESUMO

BACKGROUND: The seroprotection rate (SPR) of hepatitis B vaccination in adults is suboptimal. The aim of this study was to compare the SPR of a tri-antigenic hepatitis B vaccine (TAV), with a mono-antigenic vaccine (MAV) in adults of all ages. METHODS: This was a multicentre, double-blind, phase 3, randomised controlled trial (PROTECT) comparing the immunogenicity and safety of TAV with MAV in 28 community and hospital sites in the USA, Finland, Canada, and Belgium. Adults (aged ≥18 years) seronegative for hepatitis B virus (HBV), including those with well-controlled common chronic conditions, were randomly assigned (1:1) and stratified by study centre and age according to a web-based permuted blocked randomisation. Participants received either TAV or MAV which were administered as an intramuscular dose (1 mL) of TAV (10 µg; Sci-B-Vac, VBI Vaccines [SciVac, Rehovot, Israel]) or MAV (20 µg; Engerix-B [GlaxoSmithKline Biologicals, Rixensart, Belgium]) on days 0, 28, and 168 with six study visits and 24 weeks of follow-up after the third vaccination. Participants, investigators, and those assessing outcomes were masked to group assignment. The co-primary outcomes were to show non-inferiority of the SPRs 4 weeks after the third vaccination with TAV versus MAV in adults aged 18 years and older, as well as superiority in adults aged 45 years and older. SPR was defined as the percentage of participants attaining anti-HBs titres of 10 mIU/mL or higher. Non-inferiority of TAV to MAV was concluded if the lower limit of the 95% CI for the between-group difference was greater than -5%. Non-inferiority was assessed in the per-protocol set of participants (aged ≥18 years) and superiority was assessed in all participants (aged ≥45 years) who received at least one vaccination and had at least one evaluable immunogenicity sample after baseline (full analysis set). Safety analyses were a secondary outcome and included all participants who received at least one injection. This trial is registered at Clinicaltrials.gov (NCT03393754) and EudraCT (2017-001819-36) and is closed to new participants. FINDINGS: Between Dec 13, 2017, and April 8, 2019, 1607 participants (796 allocated to TAV and 811 allocated to MAV) were randomly assigned and distributed across age cohorts of 18-44 years (299 of 1607; 18·6%), 45-64 years (716 of 1607; 44·6%), and 65 years and older (592 of 1607; 36·8%). In participants aged 18 years and older, SPR was 91·4% (656 of 718) in the TAV group versus 76·5% (553 of 723) in the MAV group (difference 14·9%, 95% CI 11·2-18·6), showing non-inferiority in the per-protocol set. In participants aged 45 years and older, SPR was 89·4% (559 of 625) in the TAV group versus 73·1% (458 of 627) in the MAV group (difference 16·4%, 95% CI 12·2-20·7), showing superiority in the full analysis set. TAV was associated with higher rates of mild or moderate injection site pain (63·2% [503 of 796] in TAV vs 36·3% [294 of 811] in MAV), tenderness (60·8% [484 of 796] in TAV vs 34·8% [282 of 811] in MAV), and myalgia (34·7% [276 of 796] vs 24·3% [197 of 811] in MAV). Otherwise, the safety profile of TAV was similar to that of MAV. INTERPRETATION: The safety and efficacy of TAV shows its usefulness for the prevention of HBV infection in adults, including those with stable and controlled chronic conditions. FUNDING: VBI Vaccines.


Assuntos
Antígenos Virais , Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Imunogenicidade da Vacina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica , Canadá , Método Duplo-Cego , Feminino , Finlândia , Vacinas contra Hepatite B/efeitos adversos , Humanos , Esquemas de Imunização , Israel , Masculino , Pessoa de Meia-Idade , Estados Unidos , Vacinação , Adulto Jovem
6.
Front Immunol ; 12: 642546, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936059

RESUMO

Background: Vaccination is the best way to protect children under 5 years from death or disability. Children with biliary atresia (BA), which is the most common pediatric cholestatic end-stage liver disease (PELD), are more vulnerable to infectious diseases. However, the vaccination coverage and factors modulating vaccine responses in children with BA are largely unknown. Methods: In this study, 288 children (median age: 7 months) diagnosed with BA before liver transplantation were enrolled for the evaluation of vaccination status and the factors affecting the immune response to the hepatitis B (HBV) vaccine. Moreover, 49 BA children (median age: 4 months) were enrolled for flow cytometric analysis of CD4+ T cells and CD19+ B cell subsets and correlations with serum bile acid levels. Results: Generally, these children had very low routine vaccination rates for the meningococcal serogroup AC (Men AC) (41.2%), measles-mumps-rubella (MMR) (31.3%), poliomyelitis (Polio) (25.3%), hepatitis A (HAV) (25.0%), Japanese encephalitis (JE) (15.0%), diphtheria-tetanus-pertussis (DTP) (14.2%), meningococcal serogroup A (Men A) (13.5%) and varicella (VAR) (10.8%) vaccines, but not for the HBV (96.2%) and bacillus Calmette-Guérin (BCG) (84.7%) vaccines. Remarkably, 19.8% (57/288) of the patients had HBV infection. Out of 220 patients vaccinated for HBV, 113 (51.4%), 85 (38.6%) and 22 (10%) had one, two or three doses of the HBV vaccine, respectively. Furthermore, logistic regression analysis revealed that the bile acid level was an independent factor associated with poor HBV vaccine response (p = 0.03; OR = 0.394; 95% CI = 0.170-0.969). Immunophenotyping showed that bile acids were only negatively correlated with the CD19+CD27+IgG+ post-class-switched memory B cell ratio (p = 0.01). Conclusion: This study reveals the overall vaccination rates of routine vaccines in Chinese BA children are very low and the poor HBV vaccine responses are associated with bile acids, possibly via the inhibition of CD19+CD27+IgG+ post-class-switched memory B cell response. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR1800019165.


Assuntos
Linfócitos B/imunologia , Ácidos e Sais Biliares/sangue , Atresia Biliar , Linfócitos T CD4-Positivos/imunologia , Vacinas contra Hepatite B/imunologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Vacinação/estatística & dados numéricos
7.
Medicine (Baltimore) ; 100(14): e24904, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832070

RESUMO

BACKGROUND: The role of the HLA-DRB1 and HLA-DQB1 genes in the antibody response to hepatitis B (HB) vaccine has been well established; however, the involvement of the HLA-DPB1 allele in the HB vaccine immune response remained to be clarified by a systematic review. METHODS: A meta-analysis was performed in which databases were searched for relevant studies published in English or Chinese up until June 1, 2020. Six studies were identified and a total of 10 alleles were processed into statistical processing in this meta-analysis. RESULTS: Three thousand one hundred forty four subjects (including 2477 responders and 667 non-responders) were included in this research. Alleles HLA-DPB1∗02:02, DPB1∗03:01, DPB1∗04:01, DPB1∗04:02, and DPB1∗14:01 were found to be associated with a significant increase in the antibody response to HB vaccine, and their pooled odds ratios (ORs) were 4.53, 1.57, 3.33, 4.20, and 1.79, respectively; whereas DPB1∗05:01 (OR = 0.73) showed the opposite correlation. CONCLUSIONS: These findings suggested that specific HLA-DPB1 alleles are associated with the antibody response to HB vaccine.


Assuntos
Cadeias HLA-DRB1/imunologia , Vacinas contra Hepatite B/imunologia , Cadeias HLA-DRB1/genética , Anticorpos Anti-Hepatite B/imunologia , Humanos , Cobertura Vacinal/estatística & dados numéricos
8.
Front Immunol ; 12: 646677, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868282

RESUMO

Introduction: The humoral response to vaccinations varies widely between individuals. There is no data available on the correlation between responses to different vaccines. In this study, we investigated the correlation of antibody responses between routine vaccine antigens in infants. Methods: One and seven months after the 6-month vaccinations and one month after the 12-month vaccinations, antibody concentrations to diphtheria, tetanus, pertussis, polio (serotypes 1-3), Haemophilus influenzae type b (Hib), pneumococcus (13 serotypes), meningococcus C, measles, mumps and rubella were measured using fluorescent bead-based multiplex immune-assays. For the correlation of antibody responses, Spearman's rank correlation coefficients (ρ) with 95% confidence intervals (CI) were calculated between responses to each vaccine antigen. Results: The correlation between concentrations of antibodies to the vaccinations ending at 6 months of age was higher one month compared to seven months after vaccination. The strongest correlations at both time points were observed between antibody responses to different polio serotypes, certain pneumococcal serotypes and between responses to diphtheria and pneumococcal (conjugated to a diphtheria toxoid) vaccine antigens. Correlation between responses to tetanus, Hib, pertussis, polio and other vaccine antigens were weak. The correlation between antibody responses to the 12-month vaccine antigens was weaker than to the 6-month vaccine antigens and there was a negative correlation between responses to measles, mumps, rubella vaccine and non-live vaccine antigens (meningococcus C, tetanus and Hib). There was only weak correlation between antibody responses to vaccines of the same type (e.g. conjugated polysaccharide or toxoid vaccines). Conclusion: Correlation between antibody responses to similar antigens in the same vaccine (such as different serotypes of a bacteria or virus), as well as responses to antigens conjugated to similar carrier proteins, are strong. In contrast, correlation between responses to other vaccines are weak. Measuring antibody responses to one or a few vaccine antigens therefore does not offer a reliable surrogate marker of responses to unrelated vaccines.


Assuntos
Anticorpos Antibacterianos/imunologia , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Vacinas Bacterianas/imunologia , Vacinação/métodos , Vacinas Virais/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Vacinas Bacterianas/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Humanos , Imunoensaio/métodos , Lactente , Masculino , Vacina contra Coqueluche/administração & dosagem , Vacina contra Coqueluche/imunologia , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Reprodutibilidade dos Testes , Vacinas Virais/administração & dosagem
9.
Epidemiol Infect ; 149: e90, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33814028

RESUMO

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.


Assuntos
Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/imunologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Humanos , Imunogenicidade da Vacina , Lactente , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/imunologia , Segurança , Sorogrupo , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
10.
Rev. Asoc. Esp. Espec. Med. Trab ; 30(1): 57-62, mar. 2021. tab
Artigo em Espanhol | IBECS | ID: ibc-201415

RESUMO

OBJETIVOS: Evaluar la respuesta a tres dosis de la vacuna contra la Hepatitis B en profesionales de la salud. Analizar su asociación con la edad, género, tabaquismo, índice de masa corporal (IMC), presencia de enfermedades crónicas y tiempo transcurrido entre la vacunación y la medición del AcHBs. Material y MÉTODOS: estudio observacional, transversal. Muestra de trabajadores de un Hospital Universitario Portugués que realizaron medición del AcHBs en 2018 y que tenían esquema de vacunación completo. El proceso clínico individual fue consultado. Fue aplicado el Test Mann-Whitney y Chi-cuadrado y se aceptó un nivel de significancia del 5%. Resultados y CONCLUSIONES: Analizamos resultados de 181 trabajadores, edad media 32,99 años (min. 20 - max. 64), la mayoría mujeres (76,80%). El AcHBs fue positivo en 140 (77.35%) y negativo en 41 (22.65%). La presencia de enfermedades crónicas mostró asociación estadísticamente significativa con AcHBs negativo tras un esquema de vacunación completo


OBJECTIVES: evaluate the response to three doses of the Hepatitis B vaccine in healthcare workers. Analyze its association with age, gender, smoking, body mass index (BMI), presence of chronic diseases and time elapsed between vaccination and the measurement of AcHBs. MATERIAL AND METHODS: observational, cross-sectional study. Sample of workers from a Portuguese University Hospital who measured AcHBs in 2018 and who had a complete vaccination scheme. The individual clinical process was consulted. The Mann-Whitney and Chi-square test were applied and a significance level of 5% was accepted. Results and CONCLUSIONS: We analyzed the results of 181 workers, mean age 32.99 years (min. 20 - max. 64), the majority women (76.80%). The AcHBs was positive in 140 (77.35%) and negative in 41 (22.65%). The presence of chronic diseases showed a statistically significant association with negative AcHBs after a complete vaccination scheme


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Recursos Humanos em Hospital , Anticorpos Anti-Hepatite B/análise , Estudos Transversais , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/administração & dosagem , Hospitais Universitários , Fatores Sexuais , Fatores Etários , Índice de Massa Corporal , Fumar/imunologia , Portugal
11.
Front Immunol ; 12: 602826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776994

RESUMO

Idiopathic nephrotic syndrome is a childhood renal disease characterized by a damage of the glomerular filtration barrier leading to an intense leakage of proteins into the urine. This severe proteinuria causes a transient but strong reduction of serum IgG. Therefore, evaluation of vaccine competence by measuring serum levels of protective antibodies can be misleading in nephrotic syndrome, especially during the active phase of disease. To overcome this issue, in parallel to measuring serum antigen-specific IgG, we quantified by ELISPOT the number of antigen-specific memory B cells induced by previous immunization with tetanus and hepatitis B virus (HBV) in 11 steroid-sensitive nephrotic syndrome (SSNS) pediatric patients at onset before any immunosuppressive treatment (mean age 5.1±0.9 years). Five age-matched children with non-immunomediated nephro-urologic disorders were also enrolled as controls (mean age 6.9±2.3 years). Low total serum IgG levels (<520 mg/dl) were found in all the analyzed SSNS patients. In parallel, median levels of anti-tetanus and anti-HBV IgG were significantly reduced compared to controls [0.05 (0.03-0.16) vs. 0.45 (0.29-3.10) IU/ml and 0.0 (0.0-0.5) vs. 30.3 (5.5-400.8) mIU/ml, respectively; p = 0.02 for both], with serum IgG titers below protective threshold in 7/11 SSNS patients for tetanus and in 9/11 SSNS patients for HBV. In contrast, all SSNS patients had a competent B-cell response, showing an amount of total IgG-secreting B cells >1,000 counts/106 stimulated cells. The amount of anti-tetanus and anti-HBV IgG-secreting B cells was also comparable to that of controls (p = 0.24, p = 0.32, respectively), with a frequency of memory anti-tetanus and anti-HBV IgG secreting B cells >0.1% of total IgG secreting B cells. In conclusion, SSNS children at disease onset pre-immunosuppressive therapy showed a competent immune and vaccine response against tetanus and HBV, which can be correctly evaluated by quantification of antigen-specific memory B cells rather than by measuring serum IgG levels. This approach allows early identification of the impairment of immune and vaccine competence, which may derive from protracted use of different immunosuppressive drugs during disease course.


Assuntos
Anticorpos Antibacterianos , Anticorpos Anti-Hepatite B , Vacinas contra Hepatite B , Imunoglobulina G , Síndrome Nefrótica , Toxoide Tetânico , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Criança , Pré-Escolar , Feminino , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Síndrome Nefrótica/sangue , Síndrome Nefrótica/imunologia , Esteroides , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia
12.
Int J Mol Sci ; 22(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672018

RESUMO

Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) 'a' determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (ß)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate.


Assuntos
Proteínas do Capsídeo/imunologia , Citocinas/metabolismo , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Epitopos Imunodominantes/imunologia , Nodaviridae/imunologia , Transdução de Sinais/imunologia , Vacinação/métodos , Vacinas de Partículas Semelhantes a Vírus/imunologia , Animais , Anticorpos/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Temperatura Alta , Camundongos , Camundongos Endogâmicos BALB C , Células Sf9 , Spodoptera , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem
13.
MEDICC Rev ; 23(1): 21-29, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33780419

RESUMO

Hepatitis B causes liver failure, cirrhosis and cancer. It has an estimated global prevalence of 6%, and 700,000 to 1 million persons die every year of hepatitis B-related causes. In 1989, hepatitis B incidence in Cuba was 14.9 per 100,000 population. To control infection, the Genetic Engineering and Biotechnology Center and the Ministry of Public Health, both in Havana, collaborated on a joint project that first produced natural interferon and recombinant interferon alpha-2b, and later a polyethylene glycolconjugated interferon. As part of the Cuban biotechnology development strategy, the project produced a vaccine against hepatitis B in 1985. At that time, hepatitis B vaccines available elsewhere in the world were costly and inaccessible to Cubans due to the US economic and trade embargo. The Heberbiovac HB preventive vaccine was approved by the Cuban regulatory authority and added to the Cuban newborn vaccination program in 1992 after phase 1-3 clinical trials demonstrated its safety and immunogenicity. From 2001 to 2003, PAHO/WHO qualified and requalified the vaccine four times. When associated with other antigens or molecules, Heberbiovac HB provides a common platform of virus-like particles that can be used in different ways, such as in the pentavalent vaccine containing Bordetella pertussis and Haemophilus infl uenzae type b antigens and tetanus and diptheria toxoids. Thanks to this vaccine, annual incidence of acute hepatitis in Cuba has dropped from more than 2000 cases to fewer than 100, and no infections in children aged 0-15 years have been reported since 2007. It is now used in more than 30 countries, providing protective, long-lasting antibody levels with no reports of serious adverse events. Yet, hepatitis B cannot be eliminated until there are no chronic patients. The comprehensive hepatitis B control project therefore included development of a therapeutic vaccine based on Heberbiovac HB. Using its platform, researchers designed an innovative version of the vaccine that was the precursor of a therapeutic nasal/subcutaneous vaccine for chronic hepatitis B, HeberNasvac. This precursor vaccine, which combines Heberbiovac HB with a recombinant antigen from the virus nucleocapsid (rHBcAg), was patented and licensed in 2015 by the Cuban regulatory authority. This article provides an overview of the progress-to-date on the development of this therapeutic vaccine, including clinical trials (some completed and others ongoing) to determine safety, efficacy and therapeutic benefits.


Assuntos
Vacinas contra Hepatite B/imunologia , Vacinas contra Hepatite B/uso terapêutico , Hepatite B/prevenção & controle , Hepatite B/terapia , Adolescente , Criança , Pré-Escolar , Cuba , Humanos , Lactente , Recém-Nascido
14.
Vaccine ; 39(8): 1265-1271, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33516601

RESUMO

BACKGROUND: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common in sub-Saharan Africa (SSA) and can rapidly progress to cirrhosis and hepatocellular carcinoma. Recent data demonstrate ongoing HBV transmission among HIV-infected adults in SSA, suggesting that complications of HIV/HBV co-infection could be prevented with HBV vaccination. Because HBV vaccine efficacy is poorly understood among HIV-infected persons in SSA, we sought to characterize the humoral response to the HBV vaccine in HIV-seropositive Ugandan adults. METHODS: We enrolled HIV-infected adults in Kampala, Uganda without serologic evidence of prior HBV infection. Three HBV vaccine doses were administered at 0, 1 and 6 months. Anti-HBs levels were measured 4 weeks after the third vaccine dose. "Response" to vaccination was defined as anti-HBs levels ≥ 10 IU/L and "high response" as ≥ 100 IU/L. Regression analysis was used to determine predictors of response. RESULTS: Of 251 HIV-positive adults screened, 132 (53%) had no prior HBV infection or immunity and were enrolled. Most participants were women [89 (67%)]; median (IQR) age was 32 years (27-41), and 68 (52%) had received antiretroviral therapy (ART) for > 3 months. Median (IQR) CD4 count was 426 (261-583), and 64 (94%) of the 68 receiving ART had undetectable plasma HIV RNA. Overall, 117 (92%) participants seroconverted to the vaccine (anti-HBs ≥ 10 IU/L), with 109 (86%) participants having high-level response (anti-HBs ≥ 100 IU/L). In multivariate analysis, only baseline CD4 > 200 cells/mm3 was associated with response [OR = 6.97 (1.34-34.71), p = 0.02] and high-level response [OR = 4.25 (1.15-15.69)], p = 0.03]. CONCLUSION: HBV vaccination was effective in eliciting a protective humoral response, particularly among those with higher CD4 counts. Half of the screened patients did not have immunity to HBV infection, suggesting a large at-risk population for HBV infection among HIV-positive adults in Uganda. Our findings support including HBV vaccination as part of routine care among HIV-positive adults.


Assuntos
Infecções por HIV , Vacinas contra Hepatite B/imunologia , Hepatite B , Imunidade Humoral , Adulto , Feminino , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Humanos , Masculino , Uganda
15.
Int J Infect Dis ; 104: 601-609, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33508476

RESUMO

OBJECTIVES: Overt and occult hepatitis B infection (HBI) among mothers and infants were investigated, and the effectiveness of vaccination against HBI was evaluated based on transmission types. METHODS: A hospital-based cohort was built with 2,734 mothers and 330 mother-infant pairs. Their demographic data were collected. Serological HBV markers, nested-PCR for HBV genes, viral load detection, and phylogenetic analysis were done. RESULTS: The overall prevalence of HBI among mothers was 12.1% (330/2,734), with 10.4% for the overt type and 1.8% for the occult type. In 330 out of 1,650 (20%) mother-infant pairs, the overall, type-I (from overt mother to overt infant), type-II (from overt mother to occult infant), and type-Ⅲ (from occult mother to occult infant) transmissions were 1.9% (1/54), 5.6% (3/54) and 0.0% (0/7). The refinement of HBI classification improved the estimate of vaccine effectiveness against HBI from 74.4%-80.9% to 94.4%, which was more prominent for type-II. One mother-infant pair with type-II transmission shared nearly identical complete sequences. However, the high rate of lost-to-follow-up could not be ignored. CONCLUSIONS: During the transition period, HBV is mainly transmitted from the overt type of HBI mother to infant. Intensive prenatal screening for mothers is vital.


Assuntos
Vacinas contra Hepatite B , Hepatite B/epidemiologia , Hepatite B/transmissão , Transmissão Vertical de Doenças Infecciosas , Adulto , Feminino , Hepatite B/prevenção & controle , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Masculino , Mães , Filogenia , Reação em Cadeia da Polimerase , Gravidez , Diagnóstico Pré-Natal , Prevalência , Vacinação , Carga Viral
16.
Eur J Immunol ; 51(5): 1278-1281, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33459347

RESUMO

HBV vaccination is recommend for hemodialysis patients, but only 50-60% of the patients show seroconversion. HBV vaccine-induced generation of HBV reactive T and B cells could be detected regardless of their capacity to mount a serological response, indicating that patients without seroconversion are potentially protected by their HBV-reactive T cell pool.


Assuntos
Linfócitos B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Linfócitos B/metabolismo , Biomarcadores , Citocinas/metabolismo , Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Humanos , Imunofenotipagem , Diálise Renal , Linfócitos T/metabolismo , Vacinação
17.
J Leukoc Biol ; 110(5): 939-950, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33477200

RESUMO

The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, and blood samples were collected at 0, 6, 10, and 14 weeks, 6 months, 9 months, and 1 year. MDSC frequencies were quantified, and immune responses to the childhood vaccines Bacillus Calmette-Guérin (BCG), hepatitis B (HepB), and combination diphtheria, tetanus, and pertussis (dTaP) were measured by Ag-specific CD4+ T cell proliferation and interferon gamma (IFN-γ) production. Vaccine-specific Ab responses to HepB, dTaP, and Haemophilus influenzae type b (Hib) were quantified via Enzyme-Linked Immunosorbent assay (ELISA). MDSC frequency in mother-infant pairs was strongly correlated; the frequency of MDSC decreased in both mothers and infants during the months after delivery/birth; and by 1 year, infant MDSC frequencies rebounded to birth levels. Higher MDSC frequency at vaccination was associated with a lack of subsequent IFN-γ release in response to vaccine Ags, with the exception of BCG. With the exception of a weak, positive correlation between MDSC frequency at 6 weeks (time of initial vaccination) and peak Hepatitis B surface antigen Ab titer, Polymorphonuclear Myeloid-Derived Suppressor Cells (PMN-MDSC) was not correlated with T cell proliferation or Ab responses in this study. The potential for MDSC-mediated suppression of vaccine Ag-specific IFN-γ responses should be explored further, and considered when evaluating candidate infant vaccines.


Assuntos
Imunogenicidade da Vacina/imunologia , Células Supressoras Mieloides/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Vacina BCG/imunologia , Estudos de Coortes , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Vacinas contra Hepatite B/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , África do Sul
18.
Eur J Immunol ; 51(1): 167-179, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33012073

RESUMO

Circulating TFH (cTFH ) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cTFH 1, cTFH 2, cTFH 17, and cTFR cells, respectively. This CD4+ T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cTFH cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-ß-estradiol (E2) directly increased the percentage of different cTFH subsets. While E2 and progesterone (P4) increased the proportion of differentiated TFH cells derived from naïve CD4+ T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/TFH cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10+ TFR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cTFH and B cell subsets.


Assuntos
Linfócitos B/imunologia , Estradiol/sangue , Estradiol/imunologia , Imunidade Humoral , Gravidez/sangue , Gravidez/imunologia , Progesterona/sangue , Progesterona/imunologia , Células T Auxiliares Foliculares/imunologia , Adulto , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/imunologia , Diferenciação Celular , Citocinas/metabolismo , Estradiol/farmacologia , Feminino , Vacinas contra Hepatite B/imunologia , Humanos , Imunoglobulina G/biossíntese , Técnicas In Vitro , Interleucinas/biossíntese , Progesterona/farmacologia , Células T Auxiliares Foliculares/classificação , Células T Auxiliares Foliculares/citologia , Adulto Jovem
19.
J Immunoassay Immunochem ; 42(2): 121-128, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33103551

RESUMO

Hepatitis B infection has continued to be a growing global health concern in spite of the discovery and administration of hepatitis B vaccines over the years. The focus of this study was to evaluate the burden of this infection among asymptomatic pediatric population. Children, who visited the hospital between March and August 2018, were recruited into this study. Blood samples were collected after obtaining informed consent. The samples were processed and screened for HBsAg. Data were analyzed using chi-square statistic. Six (2.9%) of the 206 children in the study were positive for HBsAg. A hundred (48.5%) of the children were males and 106 (51.5%) were females in the ratio 1:1.1 (male to female). More male tested positive (4%) (4/96) than their female counterparts (1.9%) (2/104)(x2 = 0.813; p = .367). Age group 13-18 years had the highest infection rate 6.6% (4/57), followed by age group 5-12 years with 3.8% (2/50). No HBV detection was recorded among those below the age of 5 years. Patients with no vaccination history had a higher HBV infection rate (4.2%) compared with those who had been vaccinated (1.1%) (x2 = 1.164; p = .281). The study showed that HBV infection is of intermediate endemicity among the study population, a reflection of the endemic status of the infection in Nigeria. Vaccination effort among children should be sustained and intensified. We advocate for a more intensive public enlightenment on the infection especially among women of marriageable age.


Assuntos
Hepatite B/imunologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Masculino , Nigéria/epidemiologia , Estudos Retrospectivos
20.
Gut ; 70(2): 357-369, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32229546

RESUMO

OBJECTIVE: Vaccination against hepatitis B virus (HBV) confers protection from subsequent infection through immunological memory that is traditionally considered the domain of the adaptive immune system. This view has been challenged following the identification of antigen-specific memory natural killer cells (mNKs) in mice and non-human primates. While the presence of mNKs has been suggested in humans based on the expansion of NK cells following pathogen exposure, evidence regarding antigen-specificity is lacking. Here, we demonstrate the existence of HBV-specific mNKs in humans after vaccination and in chronic HBV infection. DESIGN: NK cell responses were evaluated by flow cytometry and ELISA following challenge with HBV antigens in HBV vaccinated, non-vaccinated and chronic HBV-infected individuals. RESULTS: NK cells from vaccinated subjects demonstrated higher cytotoxic and proliferative responses against autologous hepatitis B surface antigen (HBsAg)-pulsed monocyte-derived dendritic cells (moDCs) compared with unvaccinated subjects. Moreover, NK cell lysis of HBsAg-pulsed moDCs was significantly higher than that of hepatitis B core antigen (HBcAg)-pulsed moDCs (non-vaccine antigen) or tumour necrosis factor α-activated moDCs in a NKG2D-dependent manner. The mNKs response was mediated by CD56dim NK cells coexpressing CD57, CD69 and KLRG1. Further, mNKs from chronic hepatitis B patients exhibited greater degranulation against HBcAg-pulsed moDCs compared with unvaccinated or vaccinated patients. Notably, mNK activity was negatively correlated with HBV DNA levels. CONCLUSIONS: Our data support the presence of a mature mNKs following HBV antigen exposure either through vaccination or infection. Harnessing these antigen specific, functionally active mNKs provides an opportunity to develop novel treatments targeting HBV in chronic infection.


Assuntos
Vacinas contra Hepatite B/imunologia , Hepatite B/imunologia , Memória Imunológica/imunologia , Células Matadoras Naturais/imunologia , Imunidade Adaptativa/imunologia , Anticorpos Antivirais/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Antígenos da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade
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