Persistence of immunity against hepatitis A in Brazilian children vaccinated with a single dose of inactivated virus vaccine.

In 2014, the Brazilian National Immunization Program implemented the universal vaccination against the hepatitis A virus (HAV) for children aged 12 months and older, applying a single dose of the inactivated virus vaccine. It is essential to carry out follow-up studies in this population, aiming to verify the longevity of HAV immunological memory. This study evaluated the humoral and cellular immune response of a cohort of children vaccinated between 2014 and 2015, and further investigated between 2015 and 2016, and who had their initial antibody response assessed after the single dose. A second evaluation took place in January 2022. We examined 109 children out of the 252 that took part in the initial cohort. Seventy (64.2%) of them had anti-HAV IgG antibodies. Cellular immune response assays were performed in 37 anti-HAV-negative and 30 anti-HAV-positive children. Production of interferon-gamma (IFN-y) stimulated with the VP1 antigen was demonstrated in 34.3% of these 67 samples. Of the 37 negative anti-HAV samples, 12 (32.4%) produced IFN-y. Among the 30 anti-HAV-positive, 11 (36.7%) produced IFN-y. In total, 82 (76.6%) children presented some type of immune response against HAV. These findings demonstrate the persistence of immunological memory against HAV in the majority of children vaccinated between 6 and 7 years with a single dose of the inactivated virus vaccine.

Safety and immunogenicity of 17DD attenuated yellow fever vaccine in howler monkeys (Alouatta spp.).

BACKGROUND: Alouatta spp. are highly susceptible to yellow fever (YF) infection and develop an often fatal disease. The threat posed by an outbreak started in 2016 leads us to investigate vaccination as a potential tool in preventing YF in non-human primates (NHP). METHODS: Susceptible howler monkeys were immunized with three different concentrations of the human Brazilian commercial YF17DD vaccine. Post-vaccination viremia/RNAemia, immunogenicity, and safety were characterized. RESULTS: The vaccine did not produce YF clinical manifestations in any of the NHPs. After immunization, all animals seroconverted demonstrating the ability of the YF vaccine to induce humoral response in Alouatta species. CONCLUSIONS: The present work has demonstrated the safe and immunogenic profile of the existing YF 17DD vaccine in howler monkeys. This knowledge may support further studies with other susceptible monkey species and provide a possible solution for controlling epizootics and preventing the devastation of endangered species.

Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling.

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

Protective Immunity of COVID-19 Vaccination with ChAdOx1 nCoV-19 Following Previous SARS-CoV-2 Infection: A Humoral and Cellular Investigation.

Infections caused by SARS-CoV-2 induce a severe acute respiratory syndrome called COVID-19 and have led to more than six million deaths worldwide. Vaccination is the most effective preventative measure, and cellular and humoral immunity is crucial to developing individual protection. Here, we aim to investigate hybrid immunity against SARS-CoV-2 triggered by the ChAadOx1 nCoV-19 vaccine in a Brazilian cohort. We investigated the immune response from ChAadOx1 nCoV-19 vaccination in naïve (noCOVID-19) and previously infected individuals (COVID-19) by analyzing levels of D-dimers, total IgG, neutralizing antibodies (Nabs), IFN-γ (interferon-γ) secretion, and immunophenotyping of memory lymphocytes. No significant differences in D-dimer levels were observed 7 or 15 days after vaccination (DAV). All vaccinated individuals presented higher levels of total IgG or Nabs with a positive correlation (R = 0.88). Individuals in the COVID-19 group showed higher levels of antibody and memory B cells, with a faster antibody response starting at 7 DAV compared to noCOVID-19 at 15 DAV. Further, ChAadOx1 nCoV-19 vaccination led to enhanced IFN-γ production (15 DAV) and an increase in activated T CD4+ naïve cells in noCOVID-19 individuals in contrast with COVID-19 individuals. Hence, our data support that hybrid immunity triggered by ChAadOx1 nCoV-19 vaccination is associated with enhanced humoral response, together with a balanced cellular response.

Cellular and Molecular Immunology Approaches for the Development of Immunotherapies against the New Coronavirus (SARS-CoV-2): Challenges to Near-Future Breakthroughs.

The severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2), termed COVID-19, has been highlighted as the most important infectious disease of our time, without a vaccine and treatment available until this moment, with a big impact on health systems worldwide, and with high mortality rates associated with respiratory viral disease. The medical and scientific communities have also been confronted by an urgent need to better understand the mechanism of host-virus interaction aimed at developing therapies and vaccines. Since this viral disease can trigger a strong innate immune response, causing severe damage to the pulmonary tract, immunotherapies have also been explored as a means to verify the immunomodulatory effect and improve clinical outcomes, whilst the comprehensive COVID-19 immunology still remains under investigation. In this review, both cellular and molecular immunopathology as well as hemostatic disorders induced by SARS-CoV-2 are summarized. The immunotherapeutic approaches based on the most recent clinical and nonclinical studies, emphasizing their effects for the treatment of COVID-19, are also addressed. The information presented elucidates helpful insights aiming at filling the knowledge gaps around promising immunotherapies that attempt to control the dysfunction of host factors during the course of this infectious viral disease.

Cellular and Molecular Immunology Approaches for the Development of Immunotherapies against the New Coronavirus (SARS-CoV-2): Challenges to Near-Future Breakthroughs

A síndrome respiratória aguda grave causada pelo novo coronavírus (SARS-CoV-2), denominado COVID-19, foi destacada como a doença infecciosa mais importante do nosso tempo, sem vacina e sem tratamento disponível até o momento, com grande impacto nos sistemas de saúde em todo o mundo e com altas taxas de mortalidade associadas a doenças virais respiratórias. As comunidades médica e científica também foram confrontadas com a necessidade urgente de compreender melhor o mecanismo de interação vírus-hospedeiro com o objetivo de desenvolver terapias e vacinas. Uma vez que esta doença viral pode desencadear uma forte resposta imune inata, causando graves danos ao trato pulmonar, imunoterapias também têm sido exploradas como um meio para verificar o efeito imunomodulador e melhorar os resultados clínicos, enquanto a imunologia COVID-19 abrangente ainda permanece sob investigação. Nesta revisão, tanto a imunopatologia celular e molecular quanto os distúrbios hemostáticos induzidos por SARS-CoV-2 são resumidos. As abordagens imunoterapêuticas baseadas nos estudos clínicos e não clínicos mais recentes, enfatizando seus efeitos para o tratamento do COVID-19, também são abordadas. As informações apresentadas elucidam insights úteis com o objetivo de preencher as lacunas de conhecimento em torno de imunoterapias promissoras que tentam controlar a disfunção de fatores do hospedeiro durante o curso desta doença viral infecciosa.

Estabelecimento de um modelo in vitro de câncer de mama para Avaliação do Receptor Ativado por Protease (PAR) como alvo terapêutico

Câncer é um termo genérico dado para um grande grupo de doenças que podem afetar qualquer parte do corpo, cuja característica principal é o surgimento de células anormais que se dividem sem controle, podendo invadir outros tecidos em um processo denominado metástase. Na atualidade, este vem se tornando um dos mais importantes problemas de saúde pública, e neste cenário, o câncer de mama configurou-se como o segundo mais comum no mundo e o mais frequente entre as mulheres. É importante ressaltar que por se tratar de uma doença de alta complexidade, a maior parte dos tratamentos inclui a combinação de mais de uma terapia. Sendo assim, é relevante o estudo de novos alvos para desenvolvimento de drogas que auxiliem no tratamento destes tumores. Neste trabalho, escolhemos os receptores ativados por protease (PAR) como possíveis alvos terapêuticos, uma vez que sua expressão é associada a um mau prognóstico para diversos tipos de câncer. Os receptores PAR são receptores acoplados a proteína G que possuem sete domínios transmembranas. O PAR1 está diretamente relacionado ao crescimento das células tumorais, invasão e metástase de vários tipos de cânceres malignos, incluindo o câncer de mama. O medicamento Vorapaxar, utilizado para o tratamento de eventos cardiovasculares trombóticos, é um antagonista potente de PAR1 cuja ligação é irreversível. Após sua aprovação, diversos outros análogos vêm sendo desenvolvidos, dentre eles o SCH79797. Os efeitos deste inibidor sobre as vias de ativação do PAR1 ainda não foram descritos para o câncer de mama, sendo, por essa razão, objeto do nosso estudo. Nosso objetivo foi estabelecer um modelo experimental in vitro para a avaliação do receptor PAR1 como alvo terapêutico para o câncer de mama. Foram utilizadas duas linhagens celulares: a MCF-7 que expressa níveis baixíssimos do receptor PAR1 e a MCF-7 transfectada com PAR1. Foi possível demonstrar uma maior expressão do receptor PAR1 na linhagem celular MCF-7 PAR1+ em relação à MCF-7. Foi observado que a linhagem MCF-7 PAR1+ tende a promover uma maior ativação da via de sinalização ERK, comparado à linhagem MCF-7, havendo uma ligeira inibição da fosforilação de ERK no tempo de 60 minutos de incubação com SCH 79797. As células tumorais MCF-7 PAR1+ apresentaram maior capacidade proliferativa e uma inibição na proliferação desta célula, após incubação com SCH 79797. Houve um aumento na expressão de fatores de agressividade e invasividade nas células MCF-7 PAR1+ em relação às células MCF-7 avaliadas por RT-qPCR. Somente para o fator IL-8, houve inibição causada pelo SCH 79797. Foi observado também uma tendência no aumento no nível de IL-8 no sobrenadante das células MCF-7 PAR1+ avaliadas por microarranjo líquido quando comparadas com a MCF-7.