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1.
Clin Infect Dis ; 75(1): e792-e804, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34537835

RESUMO

BACKGROUND: The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial. METHODS: Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18-59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18-59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.


Assuntos
COVID-19 , Vacinas Virais , Adolescente , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Chile , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina , Imunoglobulina G , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinas de Produtos Inativados/efeitos adversos , Adulto Jovem
2.
Immunology ; 163(3): 262-277, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33638192

RESUMO

Orthohantaviruses, previously named hantaviruses, cause two emerging zoonotic diseases: haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Overall, over 200 000 cases are registered every year worldwide, with a fatality rate ranging between 0·1% and 15% for HFRS and between 20% and 40% for HCPS. No specific treatment or vaccines have been approved by the U.S. Food and Drug Administration (FDA) to treat or prevent hantavirus-caused syndromes. Currently, little is known about the mechanisms at the basis of hantavirus-induced disease. However, it has been hypothesized that an excessive inflammatory response plays an essential role in the course of the disease. Furthermore, the contributions of the cellular immune response to either viral clearance or pathology have not been fully elucidated. This article discusses recent findings relative to the immune responses elicited to hantaviruses in subjects suffering HFRS or HCPS, highlighting the similarities and differences between these two clinical diseases. Also, we summarize the most recent data about the cellular immune response that could be important for designing new vaccines to prevent this global public health problem.


Assuntos
Infecções por Hantavirus/imunologia , Orthohantavírus/fisiologia , Vacinas Virais/imunologia , Animais , Parada Cardíaca , Febre Hemorrágica com Síndrome Renal , Humanos , Imunidade Celular , Camundongos , Zoonoses Virais
3.
medRxiv ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35441164

RESUMO

Background: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. Methods: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov ( NCT04651790 ). Findings: The recruitment of participants occurred between November 27 th , 2020, until January 9 th , 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. Interpretation: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens. Funding: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

4.
Front Immunol ; 11: 569760, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362758

RESUMO

The World Health Organization (WHO) announced in March a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This new infectious disease was named Coronavirus Disease 19 (COVID-19), and at October 2020, more than 39,000,000 cases of SARS-CoV-2 have been detected worldwide leading to near 1,100,000 deaths. Clinically, COVID-19 is characterized by clinical manifestations, such as fever, dry cough, headache, and in more severe cases, respiratory distress. Moreover, neurological-, cardiac-, and renal-related symptoms have also been described. Clinical evidence suggests that migration of immune cells to the affected organs can produce an exacerbated release of proinflammatory mediators that contribute to disease and render the immune response as a major player during the development of the COVID-19 disease. Due to the current sanitary situation, the development of vaccines is imperative. Up to the date, 42 prototypes are being tested in humans in different clinical stages, with 10 vaccine candidates undergoing evaluation in phase III clinical trials. In the same way, the search for an effective treatment to approach the most severe cases is also in constant advancement. Several potential therapies have been tested since COVID-19 was described, including antivirals, antiparasitic and immune modulators. Recently, clinical trials with hydroxychloroquine-a promising drug in the beginning-were suspended. In addition, the Food and Drug Administration (FDA) approved convalescent serum administration as a treatment for SARS-CoV-2 patients. Moreover, monoclonal antibody therapy is also under development to neutralize the virus and prevent infection. In this article, we describe the clinical manifestations and the immunological information available about COVID-19 disease. Furthermore, we discuss current therapies under study and the development of vaccines to prevent this disease.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Vacinas contra COVID-19/imunologia , COVID-19/patologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Monoclonais/uso terapêutico , COVID-19/prevenção & controle , COVID-19/terapia , Feminino , Humanos , Imunização Passiva/métodos , Masculino , RNA Viral/genética , Receptores Virais/metabolismo , Linfócitos T/imunologia , Soroterapia para COVID-19
5.
Artigo em Inglês | MEDLINE | ID: mdl-32984065

RESUMO

Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) in South America is a public health threat due to the significant rate of mortality and the lack of a specific treatment. Interestingly, the virus does not produce cytopathic effect, thereby the strong antiviral immune response is suspected to contribute to pathogenesis, hence is important to understand the balance between protective and harmfully immunity. CD4+ T regulatory cells (Treg) are essential to control an exacerbated immune response. In human ANDV infection, little is known about CD4+ Treg cells, which may be involved in control immunopathology associated to the infection. In this report, we characterize the phenotype of memory CD4+ Tregs in a HCPS survivor's cohort. Based on the expression of CXCR3, CCR4, and CCR6, we identified different Th-like Treg populations in ANDV survival's PBMCs. In addition, the effect of ANDV-glycoprotein virus like particles (VLP) was determined. We demonstrated that memory CD4+ Treg from HCPS present a specific phenotype, showing higher frequency of PD-1 compared to healthy donors (HD). In addition, it was observed a decrease in the frequency of Th1-like memory CD4+ Treg in HCPS, important to highlight that this signature could be preserved even years after resolution of infection. Moreover, to gain insight in the mechanism involved, we evaluated whether ANDV-glycoprotein (GP) VLP could modulate CD4+ Treg. Interestingly, ANDV-GP VLP induced a decrease in the frequency of CXCR3 (Th1-like) and an increase in CCR4 (Th2-like) memory CD4+ Treg in both HD and HCPS PBMCs, indicating that ANDV-GP could specifically act over CXCR3 and CCR4 in CD4+ Treg. This report contributes to the study of human CD4+ Treg cells in ANDV infection.


Assuntos
Infecções por Hantavirus , Orthohantavírus , Glicoproteínas , Humanos , Fenótipo , Linfócitos T Reguladores
6.
Rev Chilena Infectol ; 33(3): 275-81, 2016 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-27598275

RESUMO

BACKGROUND: Currently in Chile, due to the frequent clinical suspicion of Hantavirus disease and the high public health impact that this causes, it is necessary to strengthen the criteria for clinical and epidemiological suspicion in the health team. OBJECTIVE: To analyze the information contained in the reports of suspected Hantavirus infection versus the confirmatory diagnosis with the reference technique, IgM capture ELISA anti-hantavirus. Material andMethods: Correlation between the information provided in notifications versus the result of confirmation was analyzed by calculating diagnostic accuracy. RESULTS: 3.4% of 1,566 patients studied (53 cases) was confirmed as SCPH. 58.6% of the analyzed notifications was incomplete. The percentage of positivity of the reference technique associated with fever, myalgia and headache was 80-85%. The presence of immunoblasts (> 10%) showed 25% sensitivity, 98% specificity, 37% PPV, 97% NPV. Thrombocytopenia exhibited 98% sensitivity, 74% specificity, 16% PPV, 100% NPV. CONCLUSION: It is necessary to reinforce the importance of comprehensive data reporting at the health system level. The presence of thrombocytopenia and immunoblasts (> 10%) is highly sensitive and specific, respectively, for detecting patients with SCPH. There is a need to develop training programs in order to optimize the suspicion of Hantavirus infection and appropriate use of health resources.


Assuntos
Notificação de Doenças/normas , Vírus Hantaan/isolamento & purificação , Síndrome Pulmonar por Hantavirus/diagnóstico , Febre Hemorrágica com Síndrome Renal/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Chile , Ensaio de Imunoadsorção Enzimática , Feminino , Síndrome Pulmonar por Hantavirus/sangue , Febre Hemorrágica com Síndrome Renal/sangue , Humanos , Imunoglobulina M/sangue , Lactente , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Valores de Referência , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Testes Sorológicos/métodos , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Adulto Jovem
7.
Rev. chil. infectol ; Rev. chil. infectol;33(3): 275-281, jun. 2016. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-791019

RESUMO

Antecedentes: Actualmente en Chile, debido a la elevada sospecha clínica de enfermedad por hantavirus y el alto impacto en salud pública que esto provoca, se hace necesario reforzar al equipo de salud, los criterios de sospecha clínica y epidemiológica de hantavirosis. Objetivo: Analizar la información contenida en las notificaciones de sospecha de infección por hantavirus versus la técnica de referencia para el diagnóstico confirmatorio de casos sospechosos, ELISA IgM de captura anti-hantavirus. Material y Método: Mediante cálculo de precisión diagnóstica se analizó la correlación que existe entre la información entregada en las notificaciones versus el resultado de la confirmación mediante la técnica de referencia. Resultados: De 1.566 pacientes estudiados 3,4% (53 casos) fue confirmado para SCPH. De las notificaciones analizadas 58,6% estaban con datos incompletos. Los porcentajes de positividad de la técnica de referencia asociada a fiebre, mialgia y cefalea, fueron de 80-85%. Destaca que la presencia de inmunoblastos (> 10%), presenta: S: 25%, E: 98%, VPP: 37%, VPN: 97%. Paratrombocitopenia se obtuvo: S: 98%, E: 74%, VPP: 16%, VPN: 100%. Conclusión: Se hace necesario reiterar a nivel del sistema sanitario chileno la importancia de contar con datos completos en los formularios de notificación. La presencia de trombocitopenia e inmunoblastos (> 10%) fue altamente sensible y especifica, respectivamente, en la detección de pacientes con SCPH. Con el fin de optimizar la sospecha de infección por hantavirus, según la definición de caso sospechoso, se plantea la necesidad de desarrollar programas de capacitación para la sospecha clínica y lectura de parámetros de laboratorio, tales como presencia de inmunoblastos en el hemograma, así como incluir un algoritmo con el fin de optimizar la sospecha y el uso adecuado de los recursos sanitarios.


Background: Currently in Chile, due to the frequent clinical suspicion of Hantavirus disease and the high public health impact that this causes, it is necessary to strengthen the criteria for clinical and epidemiological suspicion in the health team. Objective: To analyze the information contained in the reports of suspected Hantavirus infection versus the confirmatory diagnosis with the reference technique, IgM capture ELISA anti-hantavirus. Material andMethods: Correlation between the information provided in notifications versus the result of confirmation was analyzed by calculating diagnostic accuracy. Results: 3.4% of 1,566 patients studied (53 cases) was confirmed as SCPH. 58.6% of the analyzed notifications was incomplete. The percentage of positivity of the reference technique associated with fever, myalgia and headache was 80-85%. The presence of immunoblasts (> 10%) showed 25% sensitivity, 98% specificity, 37% PPV, 97% NPV. Thrombocytopenia exhibited 98% sensitivity, 74% specificity, 16% PPV, 100% NPV. Conclusion: It is necessary to reinforce the importance of comprehensive data reporting at the health system level. The presence of thrombocytopenia and immunoblasts (> 10%) is highly sensitive and specific, respectively, for detecting patients with SCPH. There is a need to develop training programs in order to optimize the suspicion of Hantavirus infection and appropriate use of health resources.


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Vírus Hantaan/isolamento & purificação , Síndrome Pulmonar por Hantavirus/diagnóstico , Notificação de Doenças/normas , Febre Hemorrágica com Síndrome Renal/diagnóstico , Padrões de Referência , Valores de Referência , Trombocitopenia/diagnóstico , Trombocitopenia/sangue , Imunoglobulina M/sangue , Ensaio de Imunoadsorção Enzimática , Testes Sorológicos/métodos , Estudos Soroepidemiológicos , Chile , Sensibilidade e Especificidade , Síndrome Pulmonar por Hantavirus/sangue , Febre Hemorrágica com Síndrome Renal/sangue , Anticorpos Antivirais/sangue
8.
Viruses ; 7(4): 2006-13, 2015 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-25912713

RESUMO

Hantavirus disease in America has been recognizable because of its rapid progression in clinical cases, occurrence in previously healthy young adults, and high case fatality rate. Hantavirus disease has been proposed now to define the diversity of clinical manifestations. Since 1995, a total of 902 cases of hantavirus pulmonary syndrome have been reported in Chile, caused by Andes virus (ANDV), with overall fatality of 32%. This report describes the sero-epidemiology of hantavirus in apparently healthy people in rural and urban slum communities from southern Chile. Ten of 934 samples yielded a positive result resulting in a seroprevalence of 1.07% (95% confidence intervals: 0.05%-2.0%). A higher proportion of positive samples was found among individuals from rural villages (1.3%) and slums (1.5%) compared with farms (0.5%). Seropositivity was associated with age (p = 0.011), low education level (p = 0.006) and occupations linked to the household (homemaker, retired, or student) (p = 0.016). No evidence of infection was found in 38 sigmodontinae rodents trapped in the peri-domestic environment. Our findings highlight that exposure risk was associated with less documented risk factors, such as women in slum and rural villages, and the occurrence of infection that may have presented as flu-like illness that did not require medical attention or was misdiagnosed.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Hantavirus/epidemiologia , Adolescente , Adulto , Idoso , Animais , Chile/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Áreas de Pobreza , Fatores de Risco , Roedores/virologia , População Rural , Estudos Soroepidemiológicos , População Urbana , Adulto Jovem
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