Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever

Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance

Cytokine profile, proliferation and phosphorylation of ERK1/2 and Akt in circulating mononuclear cells from individuals during the chronic intestinal phase of <it>Schistosomiasis mansoni</it> infection

Abstract Background The immune response to Schistosoma mansoni is characterized by a granulomatous reaction around the parasite eggs that are trapped in the host liver, and this reaction modulates the immune response during the chronic phase of the disease. The typical peripheral blood mononuclear cell (PBMC) response of patients during the chronic intestinal phase of infection is characterized by a decreased response to an S. mansoni soluble egg antigen. To obtain a greater understanding of Schistosoma infections, this study investigated the effects of the soluble egg antigen (SEA) and soluble adult worm antigen (SWAP) of S. mansoni on cellular proliferation, cytokine production, and ERK1/2 and Akt phosphorylation in PBMCs from infected (XTO) and egg-negative (NI) individuals living in the same endemic area. Methods The activation status was evaluated by cell immunophenotypic staining (cytometry). The cell proliferation assay was by CFSE method. Cytokine detection assay (Th1 and Th2) was by Cytometric Bead and Array phosphorylation status was by ELISA. Results The XTO, NI and BD (blood donor) individuals from an area not endemic for schistosomiasis were compared. The CD4+ T lymphocyte proliferation rate was lower in the XTO group, but not the NI group, after SEA stimulation compared to the BD group. The CD8+ T cell proliferation rate was lower in the XTO group in the unstimulated cultures and after both SEA and SWAP stimulation compared to the BD group. Cytokine analysis after either SEA or SWAP stimulation showed a balanced cytokine pattern in the XTO and NI groups. ERK1/2 and Akt phosphorylation were only marginally detected in all groups; however, a decrease in ERK 1/2 phosphorylation was observed in the SWAP-stimulated XTO group compared to both the NI and BD groups. Conclusions The data indicate that SEA-stimulated CD4+ T cells from infected patients have a lower proliferation rate than the same cells from the NI group. Furthermore, we observed that SWAP stimulation influences ERK1/2 phosphorylation in the XTO group.</p

Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever

Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance

Cytokine profile, proliferation and phosphorylation of ERK1/2 and Akt in circulating mononuclear cells from individuals during the chronic intestinal phase of Schistosomiasis mansoni infection

Submitted by Nuzia Santos ([email protected]) on 2014-06-16T12:44:46Z No. of bitstreams: 1 Cytokine profile.pdf: 3149759 bytes, checksum: cf43916157d8279f1d5361396fd1143b (MD5)Made available in DSpace on 2014-06-16T12:44:46Z (GMT). No. of bitstreams: 1 Cytokine profile.pdf: 3149759 bytes, checksum: cf43916157d8279f1d5361396fd1143b (MD5) Previous issue date: 2012Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Escola de Enfermagem. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais.Escola de Enfermagem. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Brasilia, DF, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Clínica Médica, Cirurgia. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Cirurgia. Belo Horizonte, MG, BrazilBackground :The immune response to Schistosoma mansoni is characterized by a granulomatous reaction around the parasite eggs that are trapped in the host liver, and this reaction modulates the immune response during the chronic phase of the disease. The typical peripheral blood mononuclear cell (PBMC) response of patients during the chronic intestinal phase of infection is characterized by a decreased response to an S. mansoni soluble egg antigen. To obtain a greater understanding of Schistosoma infections, this study investigated the effects of the soluble egg antigen (SEA) and soluble adult worm antigen (SWAP) of S. mansoni on cellular proliferation, cytokine production, and ERK1/2 and Akt phosphorylation in PBMCs from infected (XTO) and egg-negative (NI) individuals living in the same endemic area. Methods : The activation status was evaluated by cell immunophenotypic staining (cytometry). The cell proliferation assay was by CFSE method. Cytokine detection assay (Th1 and Th2) was by Cytometric Bead and Array phosphorylation status was by ELISA. Results : The XTO, NI and BD (blood donor) individuals from an area not endemic for schistosomiasis were compared. The CD4+ T lymphocyte proliferation rate was lower in the XTO group, but not the NI group, after SEA stimulation compared to the BD group. The CD8+ T cell proliferation rate was lower in the XTO group in the unstimulated cultures and after both SEA and SWAP stimulation compared to the BD group. Cytokine analysis after either SEA or SWAP stimulation showed a balanced cytokine pattern in the XTO and NI groups. ERK1/2 and Akt phosphorylation were only marginally detected in all groups; however, a decrease in ERK 1/2 phosphorylation was observed in the SWAP-stimulated XTO group compared to both the NI and BD groups. Conclusions : The data indicate that SEA-stimulated CD4+ T cells from infected patients have a lower proliferation rate than the same cells from the NI group. Furthermore, we observed that SWAP stimulation influences ERK1/2 phosphorylation in the XTO group

Age-related changes in hookworm infection, anaemia and iron deficiency in an area of high Necator americanus hookworm transmission in south-eastern Brazil.

Surprisingly few detailed age-stratified data exist on the epidemiology of hookworm and iron status, especially in Latin America. We present data from a cross-sectional survey examining 1332 individuals aged 0-86 years from a community in south-east Brazil for hookworm, anaemia and iron deficiency. Sixty-eight percent of individuals were infected with the human hookworm Necator americanus. The force of infection (lambda=0.354) was similar to estimates from other areas of high hookworm transmission. Individuals from poorer households had significantly higher prevalence and intensity of infection than individuals from better-off households. The prevalence of anaemia, iron deficiency and iron-deficiency anaemia was 11.8%, 12.7% and 4.3%, respectively. Anaemia was most prevalent among young children and the elderly. Univariate analysis showed that haemoglobin and serum ferritin were both significantly negatively associated with hookworm intensity among both school-aged children and adults. Multivariate analysis showed that, after controlling for socio-economic status, iron indicators were significantly associated with heavy hookworm infection. Our results indicate that, even in areas where there is a low overall prevalence of anaemia, hookworm can still have an important impact on host iron status, especially in school-aged children and the elderly

17DD and 17D-213/77 yellow fever substrains trigger a balanced cytokine profile in primary vaccinated children

Submitted by Nuzia Santos ([email protected]) on 2014-03-07T13:46:37Z No. of bitstreams: 1 17DD.pdf: 2852641 bytes, checksum: e43b3e257ffaa87a20d7866b9fdc814d (MD5)Made available in DSpace on 2014-03-07T13:46:37Z (GMT). No. of bitstreams: 1 17DD.pdf: 2852641 bytes, checksum: e43b3e257ffaa87a20d7866b9fdc814d (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrasilUniversidade Federal de Ouro Preto. Núcleo de Pesquisas em Ciências Biológicas. Ouro Preto, MG, BrasilUniversidade Federal de Ouro Preto. Núcleo de Pesquisas em Ciências Biológicas. Ouro Preto, MG, BrasilFundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos, Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos, Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos, Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos, Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos, Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos, Bio-Manguinhos. Rio de Janeiro, RJ, BrasilGoverno do Estado de Minas Gerais. Secretaria de Estado de Saúde. Belo Horizonte, MG, BrasilGoverno do Estado de Minas Gerais. Secretaria de Estado de Saúde. Belo Horizonte, MG, BrasilUniversidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Hospital das Clínicas. Ribeirão Preto, SP, BrasilFundação Oswaldo Cruz. Diretoria Regional de Brasília. Brasília, DF, BrasilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Propedêutica Complementar. Belo Horizonte, MG, BrasilBACKGROUND: This study aimed to compare the cytokine-mediated immune response in children submitted to primary vaccination with the YF-17D-213/77 or YF-17DD yellow fever (YF) substrains. METHODS: A non-probabilistic sample of eighty healthy primary vaccinated (PV) children was selected on the basis of their previously known humoral immune response to the YF vaccines. The selected children were categorized according to their YF-neutralizing antibody titers (PRNT) and referred to as seroconverters (PV-PRNT(+)) or nonseroconverters (PV-PRNT(-)). Following revaccination with the YF-17DD, the PV-PRNT(-) children (YF-17D-213/77 and YF-17DD groups) seroconverted and were referred as RV-PRNT(+). The cytokine-mediated immune response was investigated after short-term in vitro cultures of whole blood samples. The results are expressed as frequency of high cytokine producers, taking the global median of the cytokine index (YF-Ag/control) as the cut-off. RESULTS: The YF-17D-213/77 and the YF-17DD substrains triggered a balanced overall inflammatory/regulatory cytokine pattern in PV-PRNT(+), with a slight predominance of IL-12 in YF-17DD vaccinees and a modest prevalence of IL-10 in YF-17D-213/77. Prominent frequency of neutrophil-derived TNF-α and neutrophils and monocyte-producing IL-12 were the major features of PV-PRNT(+) in the YF-17DD, whereas relevant inflammatory response, mediated by IL-12(+)CD8(+) T cells, was the hallmark of the YF-17D-213/77 vaccinees. Both substrains were able to elicit particular but relevant inflammatory events, regardless of the anti-YF PRNT antibody levels. PV-PRNT(-) children belonging to the YF-17DD arm presented gaps in the inflammatory cytokine signature, especially in terms of the innate immunity, whereas in the YF-17D-213/77 arm the most relevant gap was the deficiency of IL-12-producing CD8(+)T cells. Revaccination with YF-17DD prompted a balanced cytokine profile in YF-17DD nonresponders and a robust inflammatory profile in YF-17D-213/77 nonresponders. CONCLUSION: Our findings demonstrated that, just like the YF-17DD reference vaccine, the YF-17D-213/77 seed lot induced a mixed pattern of inflammatory and regulatory cytokines, supporting its universal use for immunization

Short-lived immunity after 17DD Yellow Fever single dose indicates that booster vaccination may be required to guarantee protective immunity in children

Submitted by Priscila Nascimento ([email protected]) on 2019-10-01T19:14:22Z No. of bitstreams: 1 Short-Lived_Immunity_After_17DD_Yellow_Fever_Singl.pdf: 3383889 bytes, checksum: 0a90002bb16cb94aad75a9789f4bd242 (MD5)Approved for entry into archive by Priscila Nascimento ([email protected]) on 2019-10-01T19:54:22Z (GMT) No. of bitstreams: 1 Short-Lived_Immunity_After_17DD_Yellow_Fever_Singl.pdf: 3383889 bytes, checksum: 0a90002bb16cb94aad75a9789f4bd242 (MD5)Made available in DSpace on 2019-10-01T19:54:22Z (GMT). No. of bitstreams: 1 Short-Lived_Immunity_After_17DD_Yellow_Fever_Singl.pdf: 3383889 bytes, checksum: 0a90002bb16cb94aad75a9789f4bd242 (MD5) Previous issue date: 2019Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Secretaria Municipal de Saúde de Belo Horizonte. Belo Horizonte, MG, Brasil.Secretaria do Estado de Saúde de Minas Gerais. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.Universidade de Brasília. Faculdade de Medicina. Brasília, DF, Brasil.Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Imunização e Doenças Transmissíveis. Brasília, DF, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Programa Nacional de Imunizações. Brasília, DF, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.A vacinação contra a febre amarela (YF) é recomendada para pessoas que vivem em áreas endêmicas e representa a estratégia mais eficaz para reduzir o risco de infecção. Estudos anteriores alertaram que os regimes de reforço devem ser considerados para garantir a persistência a longo prazo dos componentes de memória específicos da 17DD-YF em adultos que vivem em áreas com circulação do vírus da YF. Considerando as menores taxas de soroconversão observadas em crianças (9 a 12 meses de idade) em comparação aos adultos, este estudo foi desenvolvido para acessar a duração da imunidade em crianças vacinadas em dose única em um período de 10 anos de seção transversal . Os níveis de anticorpos neutralizantes (PRNT) e o status fenotípico / de memória funcional das células T e B foram medidos no início, 30 a 45 dias, 1, 2, 4, 7 e 10 anos após a vacinação primária. Os resultados revelaram que uma dose única induziu 85% de soropositividade entre 30 e 45 dias e uma diminuição progressiva dependente do tempo foi observada em apenas 2 anos e diminui para valores críticos (abaixo de 60%) em períodos de tempo ≥ 4 anos . Além disso, a imunidade celular específica de YF de curta duração, mediada pelas células T e B de memória, também foi observada após 4 anos. A análise de probabilidade prevista e a memória resultante enfatizam que os correlatos de proteção (PRNT; células T CD8 + com memória efetiva; células B com memória não clássica) diminuem para valores críticos dentro de ≥4 anos após a vacinação primária. Juntos, esses resultados demonstram claramente o declínio da resposta da memória específica da 17DD-YF ao longo do tempo em crianças vacinadas principalmente entre 9 e 12 meses de idade e suportam a necessidade de um regime de reforço para garantir a persistência a longo prazo dos componentes da memória para crianças que vivem em áreas com alto risco de transmissão YF.The Yellow Fever (YF) vaccination is recommended for people living in endemic areas and represents the most effective strategy to reduce the risk of infection. Previous studies have warned that booster regimens should be considered to guarantee the long-term persistence of 17DD-YF-specific memory components in adults living in areas with YF-virus circulation. Considering the lower seroconversion rates observed in children (9–12 months of age) as compared to adults, this study was designed in order to access the duration of immunity in single-dose vaccinated children in a 10-years cross-sectional time-span. The levels of neutralizing antibodies (PRNT) and the phenotypic/functional memory status of T and B-cells were measured at a baseline, 30–45 days, 1, 2, 4, 7, and 10 years following primary vaccination. The results revealed that a single dose induced 85% of seropositivity at 30–45 days and a progressive time-dependent decrease was observed as early as 2 years and declines toward critical values (below 60%) at time-spans of ≥4-years. Moreover, short-lived YF-specific cellular immunity, mediated by memory T and B-cells was also observed after 4-years. Predicted probability and resultant memory analysis emphasize that correlates of protection (PRNT; effector memory CD8+ T-cells; non-classical memory B-cells) wane to critical values within ≥4-years after primary vaccination. Together, these results clearly demonstrate the decline of 17DD-YF-specific memory response along time in children primarily vaccinated at 9–12 months of age and support the need of booster regimen to guarantee the long-term persistence of memory components for children living in areas with high risk of YF transmission

Multi-parameter approach to evaluate the timing of memory status after 17DD-YF primary vaccination

<div><p>In this investigation, machine-enhanced techniques were applied to bring about scientific insights to identify a minimum set of phenotypic/functional memory-related biomarkers for post-vaccination follow-up upon yellow fever (YF) vaccination. For this purpose, memory status of circulating T-cells (Naïve/early-effector/Central-Memory/Effector-Memory) and B-cells (Naïve/non-Classical-Memory/Classical-Memory) along with the cytokine profile (IFN/TNF/IL-5/IL-10) were monitored before-NV(day0) and at distinct time-points after 17DD-YF primary vaccination—PV(day30-45); PV(year1-9) and PV(year10-11). A set of biomarkers (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL-5CD8; TNFCD4; IFNCD8; TNFCD8; IL-5CD19; IL-5CD4) were observed in PV(day30-45), but not in NV(day0), with most of them still observed in PV(year1-9). Deficiencies of phenotypic/functional biomarkers were observed in NV(day0), while total lack of memory-related attributes was observed in PV(year10-11), regardless of the age at primary vaccination. Venn-diagram analysis pre-selected 10 attributes (eEfCD4, EMCD4, CMCD19, EMCD8, IFNCD4, IL-5CD8, TNFCD4, IFNCD8, TNFCD8 and IL-5CD4), of which the overall mean presented moderate accuracy to discriminate PV(day30-45)&PV(year1-9) from NV(day0)&PV(year10-11). Multi-parameter approaches and decision-tree algorithms defined the EMCD8 and IL-5CD4 attributes as the top-two predictors with moderated performance. Together with the PRNT titers, the top-two biomarkers led to a resultant memory status observed in 80% and 51% of volunteers in PV(day30-45) and PV(year1-9), contrasting with 0% and 29% found in NV(day0) and PV(year10-11), respectively. The deficiency of memory-related attributes observed at PV(year10-11) underscores the conspicuous time-dependent decrease of resultant memory following17DD-YF primary vaccination that could be useful to monitor potential correlates of protection in areas under risk of YF transmission.</p></div