Recombinant Bacillus Calmette-Guérin Expressing SARS-CoV-2 Chimeric Protein Protects K18-hACE2 Mice against Viral Challenge.

COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette-Guérin (BCG), the existing tuberculosis vaccine, is known to induce heterologous effects over other infections due to trained immunity and has been proposed to be a potential strategy against SARS-CoV-2 infection. In this report, we constructed a recombinant BCG (rBCG) expressing domains of the SARS-CoV-2 nucleocapsid and spike proteins (termed rBCG-ChD6), recognized as major candidates for vaccine development. We investigated whether rBCG-ChD6 immunization followed by a boost with the recombinant nucleocapsid and spike chimera (rChimera), together with alum, provided protection against SARS-CoV-2 infection in K18-hACE2 mice. A single dose of rBCG-ChD6 boosted with rChimera associated with alum elicited the highest anti-Chimera total IgG and IgG2c Ab titers with neutralizing activity against SARS-CoV-2 Wuhan strain when compared with control groups. Importantly, following SARS-CoV-2 challenge, this vaccination regimen induced IFN-γ and IL-6 production in spleen cells and reduced viral load in the lungs. In addition, no viable virus was detected in mice immunized with rBCG-ChD6 boosted with rChimera, which was associated with decreased lung pathology when compared with BCG WT-rChimera/alum or rChimera/alum control groups. Overall, our study demonstrates the potential of a prime-boost immunization system based on an rBCG expressing a chimeric protein derived from SARS-CoV-2 to protect mice against viral challenge.

Recombinant BCG-LTAK63 Vaccine Candidate for Tuberculosis Induces an Inflammatory Profile in Human Macrophages.

Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from Escherichia coli (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and Mycobacterium tuberculosis (Mtb) H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels. The rBCG-LTAK63-infected M1 macrophages more profoundly upregulated interferon-inducible genes such as IFIT3, OAS3, and antimicrobial gene CXCL9 compared to BCG, and induced higher levels of inflammatory cytokines such as IL-12(p70), TNF-ß, and IL-15. The rBCG-LTAK63-infected M2 macrophages more extensively upregulated transcripts of inflammation-related genes, TAP1, GBP1, SLAMF7, TNIP1, and IL6, and induced higher levels of cytokines related to inflammation and tissue repair, MCP-3 and EGF, as compared to BCG. Thus, our data revealed an important signature of immune responses induced in human macrophages by rBCG-LTAK63 associated with increased inflammation, activation, and tissue repair, which may be correlated with a protective immune response against TB.

SARS-CoV-2 vaccine development and how Brazil is contributing.

The SARS-CoV-2 coronavirus pandemic calls for coordinated efforts by the scientific community for the development of vaccines. The most advanced strategies have focused on modifications of technologies that were already under development for other viruses, such as SARS, MERS, and even Influenza. Classic and new technologies, such as inactivated and attenuated viruses (non-replicative and replicative), DNA and mRNA vaccines, and nanoparticles containing SARS-CoV-2 antigens, are some of the strategies currently investigated. Although there is a very high expectation for the effectiveness of the most advanced vaccine candidates, there are still no established correlates of protection. Previous experience in vaccine development for other pathogens shows that differences in vaccine formulation can result in diverse immune responses and consequently, different protective properties. Therefore the importance of continuing investigations on a broad range of strategies. Expertise in vaccine development in Brazil was refocused to the new coronavirus. Impressive collaboration between institutions will support further developments until we have available a safe, effective, and economically viable vaccine. Established competence and collaborations will allow preparedness for future challenges and can also be used to address local issues as neglected infectious diseases.

Unwrapping the long-term impacts of COVID-19 pandemic on Brazilian academic mothers: the urgency of short, medium, and long-term measures.

Since the beginning of the COVID-19 pandemic, publications have highlighted the disproportionate impact of the COVID-19 pandemic on academic mothers, mostly focusing on the impact of social distancing and quarantine. A few months later, despite the lack of effective vaccines or therapeutics in sight, many economic activities are being resumed. Nurseries and schools are expected to be among the latest to reopen, which will amplify the impacts of the pandemic on academic mothers. In this letter, we unwrap the pandemic impacts on academic mothers and describe a set of specific short-, medium- and long-term policies that, if implemented, could reduce setbacks for gender equality during the pandemic and can help to level the playing field for academic mothers.

Vaccines for COVID-19: perspectives from nucleic acid vaccines to BCG as delivery vector system.

This article discusses standard and new disruptive strategies in the race to develop an anti-COVID-19 vaccine. We also included new bioinformatic data from our group mapping immunodominant epitopes and structural analysis of the spike protein. Another innovative approach reviewed here is the use of BCG vaccine as priming strategy and/or delivery system expressing SARS-CoV-2 antigens.

Phylloseptin-1 is Leishmanicidal for Amastigotes of Leishmania amazonensis Inside Infected Macrophages

Leishmania protozoans are the causal agents of neglected diseases that represent an important public health issue worldwide. The growing occurrence of drug-resistant strains of Leishmania and severe side effects of available treatments represent an important challenge for the leishmaniases treatment. We have previously reported the leishmanicidal activity of phylloseptin-1 (PSN-1), a peptide found in the skin secretion of Phyllomedusa azurea (=Pithecopus azureus), against Leishmania amazonensis promastigotes. However, its impact on the amastigote form of L. amazonensis and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of L. amazonensis inside macrophages infected in vitro. We assessed the production of hydrogen peroxide and nitric oxide, as well as the levels of inflammatory and immunomodulatory markers (TGF-ß, TNF-αand IL-12), in infected and non-infected macrophages treated with PSN-1. Treatment with PSN-1 decreased the number of infected cells and the number of ingested amastigotes per cell when compared with the untreated cells. At 32 µM (64 µg/mL), PSN-1 reduced hydrogen peroxide levels in both infected and uninfected macrophages, whereas it had little effect on NO production or TGF-ß release. The effect of PSN-1 on IL-12 and TNF-αsecretion depended on its concentration, but, in general, their levels tended to increase as PSN-1 concentration increased. Further in vitro and in vivo studies are needed to clarify the mechanisms of action of PSN-1 and its interaction with the immune system aiming to develop pharmacological applications.

Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil. / Medidas de distanciamento social no controle da pandemia de COVID-19: potenciais impactos e desafios no Brasil.

The COVID-19 pandemic has challenged researchers and policy makers to identify public safety measures forpreventing the collapse of healthcare systems and reducingdeaths. This narrative review summarizes the available evidence on the impact of social distancing measures on the epidemic and discusses the implementation of these measures in Brazil. Articles on the effect of social distancing on COVID-19 were selected from the PubMed, medRXiv and bioRvix databases. Federal and state legislation was analyzed to summarize the strategies implemented in Brazil. Social distancing measures adopted by the population appear effective, particularly when implemented in conjunction with the isolation of cases and quarantining of contacts. Therefore, social distancing measures, and social protection policies to guarantee the sustainability of these measures, should be implemented. To control COVID-19 in Brazil, it is also crucial that epidemiological monitoring is strengthened at all three levels of the Brazilian National Health System (SUS). This includes evaluating and usingsupplementary indicators to monitor the progression of the pandemic and the effect of the control measures, increasing testing capacity, and making disaggregated notificationsand testing resultstransparentand broadly available.

A pandemia de COVID-19 tem desafiado pesquisadores e gestores a encontrar medidas de saúde pública que evitem o colapso dos sistemas de saúde e reduzam os óbitos. Esta revisão narrativa buscou sistematizar as evidências sobre o impacto das medidas de distanciamento social na epidemia de COVID-19 e discutir sua implementação no Brasil. Foram triados artigos sobre o efeito do distanciamento social na COVID-19 no PubMed, medRXiv e bioRvix, e analisados atos do poder público nos níveis federal e estadual para sumarizar as estratégias implementadas no Brasil. Os achados sugerem que o distanciamento social adotado por população é efetivo, especialmente quando combinado ao isolamento de casos e à quarentena dos contatos. Recomenda-se a implementação de medidas de distanciamento social e de políticas de proteção social para garantir a sustentabilidade dessas medidas. Para o controle da COVID-19 no Brasil, é imprescindível que essas medidas estejam aliadas ao fortalecimento do sistema de vigilância nos três níveis do SUS, que inclui a avaliação e uso de indicadores adicionais para monitorar a evolução da pandemia e o efeito das medidas de controle, a ampliação da capacidade de testagem, e divulgação ampla e transparente das notificações e de testagem desagregadas.

Cloth masks in public places: an essential intervention to prevent COVID-19 in Brazil. / Máscaras de tecido em locais públicos: intervenção essencial na prevenção da COVID-19 no Brasil.

There is increasing evidence that the use of masks is an indispensable protective measure against COVID-19, given the high transmissibility of the new coronavirus through the respiratory system, including by asymptomatic individuals. The use of cloth masks in public places has been established as a protective measure to be adopted alongside social distancing and hand hygiene. This narrative review aims to systematize the scientific evidence that informs the widespread use of cloth masks as a preventive measure against COVID-19 and to describe the evolution of positions contrary to or in favor of its use outside the home, in view of the advance of the new coronavirus pandemic globally. The scientific articles, technical notes, governmental decrees and other documents analyzed indicate that widespread use of masks has the potential to reduce the spread of the new coronavirus. We recommend that the Brazilian government adopt strategies to increase the supply of reusable cloth masks to the public, especially to vulnerable populations and to support studies on the impact of this measure to control the pandemic in the country. Finally, it is imperative to ensure that use of masks does not exacerbate stigmatization of racial groups that already face prejudice.

Acumulam-se evidências de que o uso de máscaras é uma medida indispensável de proteção à COVID-19, devido ao alto poder de transmissão do novo coronavírus por via respiratória, inclusive por indivíduos assintomáticos. Por sua vez, o uso das máscaras de tecido em locais públicos tem se consolidado como medida adicional de proteção às medidas de distanciamento social e higienização das mãos. Objetivou-se sistematizar as evidências científicas que justificam o amplo uso de máscaras de tecido como prevenção à COVID-19 e descrever a evolução dos posicionamentos contrários ou favoráveis ao seu uso em ambientes extradomiciliares, diante do avanço da pandemia do novo coronavírus pelo mundo. A triagem de artigos e documentos oficiais do Brasil e de outros países indica que o uso de máscaras em locais públicos tornou-se uma intervenção essencial graças ao potencial de reduzir a velocidade de propagação do novo coronavírus. Recomenda-se que o poder público adote estratégias para aumentar a oferta deste produto e fomente estudos para avaliação do impacto da medida no controle da pandemia no Brasil. É imperativo assegurar disponibilidade de máscaras a grupos socioeconomicamente desfavorecidos e garantir que determinados grupos raciais não sejam estigmatizados diante do uso de máscaras em ambientes extradomiciliares.