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The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a SARS-CoV-2 spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose vaccinations. Dose-dependent SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.

B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna's mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1–4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5–7 and nonhuman primates8–10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11–13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis., A single immunization with an adenovirus vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein induces protection against SARS-CoV-2-induced weight loss, pneumonia and mortality in hamsters.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged and may pose a threat to both the efficacy of vaccines based on the original WA1/2020 strain as well as to natural immunity induced by infection with earlier SARS-CoV-2 variants. We sought to explore unanswered questions of how mutations in the spike of circulating SARS-CoV-2 variants, which have been shown to partially evade neutralizing antibodies, impact natural and vaccine-induced immunity. We adapted a Syrian hamster model of moderate to severe clinical disease for two variant strains of SARS-CoV-2: B.1.1.7 (α variant) and B.1.351 (β variant). We then assessed the protective efficacy conferred by either natural immunity from WA1/2020 infection or by vaccination with a single dose of the adenovirus serotype 26 vaccine Ad26.COV2.S. Primary infection with the WA1/2020 strain provided potent protection against weight loss and viral replication in lungs following re-challenge with WA1/2020, B.1.1.7, or B.1.351 14 days later. Ad26.COV2.S induced cross-reactive binding and neutralizing antibodies that were reduced against the B.1.351 strain compared with WA1/2020, but nevertheless still provided robust protection against B.1.351 challenge, as measured by weight loss and pathology scoring in the lungs. Taken together, these data support hamsters as a pre-clinical model to study protection against emerging variants of SARS-CoV-2 conferred by prior infection or vaccination.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs).1 Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access.2 Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing costs.3 These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples.4–6 Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2.7,8 Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

BackgroundVaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351.MethodsNonhuman primates received 30 or 100 µg of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 µg at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge.ResultsEight weeks post-boost, 100 µg x2 of mRNA-1273 induced reciprocal ID50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 µg x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 µg. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 µg x2 of mRNA-1273, and there was a ∼2-log reduction in sgRNA in NHP that received two doses of 30 µg compared to controls. In nasal swabs, there was a 1-log10 reduction observed in the 100 µg x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge.ConclusionsImmunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.

Here we have employed SynCon® design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants of concern (VOC). Compared to WT and VOC-matched vaccines which showed reduced cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster challenge model demonstrated that INO-4802 conferred superior protection following intranasal B.1.351 challenge. Protection against weight loss associated with WT, B.1.1.7, P.1 and B.1.617.2 challenge was also demonstrated. Vaccinated hamsters showed enhanced humoral responses against VOC in a heterologous WT vaccine prime and INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOC as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT-matched vaccines.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 – 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.One-Sentence SummarymRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain subunits with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results show that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage (lung and nares) for protected animals, compared with ~10% weight loss, higher viral loads and tissue damage in unprotected animals. Furthermore, the data show that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a long history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.

Significance Most of the global population resides in low- and middle-income countries, where current vaccines for COVID-19 remain largely unavailable. For the COVID-19 pandemic, the world will need access to >10 billion doses of vaccines, or more than double the annual volume of vaccines for all other diseases. Many vaccine candidates use the SARS-CoV-2 receptor-binding domain (RBD) antigen. Here, we present an engineered RBD with improved production titers in Pichia pastoris, a yeast commonly used for large-scale, low-cost manufacturing by vaccine manufacturers. The modified RBD also raises an enhanced immune response in mice relative to the Wuhan-Hu-1 sequence used in current candidates. These combined traits make it a promising candidate for next-generation vaccines addressing emerging variants of the virus., Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

Coconut water is widely consumed and appreciated due its sensory, nutritional, and functional characteristics. Despite being widely consumed, this beverage has a short shelf life that can be improved through processing technologies including non-thermal technologies. Although this processing is promising, it also can generate toxic bioactive compounds of natural and synthetic origin. Their safety has been long discussed, and concern for human food security is now clearly manifested by warnings added on products labels. The aim of this work was to evaluate the toxic and the protective effect of natural and processed coconut water by non-thermal technologies against oxidative stress in brine shrimp (Artemia salina). For acute toxicity test, A. salina nauplii instar II were exposed to different concentrations and ozone-processed (OTCW), plasma-processed (PTCW), and ultrasound-processed (UTCW) coconut water. The non-processed sample was the negative control. By the end of experiment (48 h), dead nauplii were counted and investigated under optical and electron microscopy. The protective effect was evaluated against H2O2 and morphological changes were also investigated. Coconut water treated with plasma and ultrasound was not toxic to Artemia salina nauplii at 10, 100, or 1000 μg mL−1; however, ozone-treated artificial seawater caused a mild toxicity to nauplii exposed to 1000 μg mL−1. All coconut water samples, included untreated samples, presented protective effect against oxidative stress caused by H2O2 reaching levels of 87.5% protection compared to control (24 h of experiment).

Summary SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19., Highlights • mRNA vaccines induce robust type 1 CD4+ and CD8+ T cells in the spleen and lung • Vaccine-induced T cells readily exit the vasculature and enter the lung parenchyma • mRNA vaccines elicit strong long-lived plasma cell and memory B cell responses • mRNA vaccines induce antibodies with potent anti-SARS-CoV-2 neutralization activity, SARS-CoV-2 mRNA-based vaccines are among the most promising vaccine candidates against COVID-19. Laczkó et al. evaluate two nucleoside-modified mRNA vaccine candidates in mice and demonstrate that they induce potent T and B cell immune responses and high levels of neutralizing antibodies after administration of a single vaccine dose.

With the job market becoming increasingly competitive, the student of the administration course has been searching more and more for ways to improve their results and one of the most efficient ways to do this is by developing new skills. In this context, the Coaching process is presented as a strategy, a management tool capable of contributing to the development of behavioral skills such as discipline, focus, and consistency. Given this scenario, this work aims to propose the Coaching process as a tool for the development of new skills in students of the administration course. Initially, bibliographic research was done, presenting a theoretical approach to the context of Coaching. Research is used in books, periodicals, Scielo-based scientific articles, and other electronic sources. Therefore, the problem involving this research is to demonstrate how the Coaching process can leverage the personal and professional development of students in the administration course.

An urgent global quest for effective therapies to prevent and treat COVID-19 disease is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques and golden hamsters and demonstrate that REGN-COV-2 can greatly reduce virus load in lower and upper airway and decrease virus induced pathological sequalae when administered prophylactically or therapeutically. Our results provide evidence of the therapeutic potential of this antibody cocktail.

In this study, the effect of plasma and ozone processing on the quality of coconut water was evaluated. For ozone processing, the samples were submitted to different ozone loads and temperatures. For atmospheric cold plasma processing (ACP), samples were exposed to plasma under different frequencies and voltages. The coconut water pH, soluble solids, titratable acidity, color, total phenolic content, and enzymatic activity were determined before and after treatments. The main compounds were also determined by NMR spectroscopy and chemometric analysis. Both processes did not change the pH values, total soluble solids, titratable acidity, and color. Chemometrics analysis of 1H NMR dataset showed no relevant changes after the processing. All ozone treatments promoted complete inactivation of POD activity and did not affect the content of phenolic compounds. After ACP, the smallest POD residual activity was observed when higher frequencies were applied, and slight changes in phenolic compounds content were observed.

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19., Graphical Abstract, Highlights • SARS-CoV-2 infection leads to macrophage infiltrates in the lung of infected macaques • SARS-CoV-2 upregulates proinflammatory cytokines and ISGs in macaques • SARS-CoV-2 upregulates complement and coagulation cascade in macaques • SARS-CoV-2 infection leads to endothelial damage and thrombosis in macaques, Aid et al. show that SARS-CoV-2 causes endothelial disruption and vascular thrombosis in both human and rhesus macaques lungs by inducing an upregulation of proinflammatory cytokines. Using an approach that combines histopathology and multiomics in macaques, they show the progression to vascular disease over time, which involves complement, macrophage, cytokine, and thrombosis cascades.

Second semester University: Panteion University, Athens, This thesis evaluates whether the Inter-American System for Protection of Human Rights should allow all criminal convicts to take vote or not. The objective is to highlight the clear need for change and the outdated and social troubling standing regarding felony disenfranchisement in Latin America. For this purpose, the research relies on a multidisciplinary investigation to analyse felony disenfranchisement policies and its operation in the region under the scrutiny of the America Convention on Human Rights. While Latin American countries should ungently be engaged in policies to promote inclusion and social rehabilitation of prisoners, criminal disenfranchisement, as a mere punitive measure, is openly embraced by the America Convention on Human Rights (Article 23.2). Once is clear the social impacts of felony disenfranchisement and its critical and contradictory establishment under the Inter-America System for Protection of Human Rights, the research uncovers the impropriety of the denial of prisoners ‘voting rights under international human rights law. Even though criminal disenfranchisement policies seem to be a countermeasure to develop human rights’ protection, the Inter-American System does not review the matter. Keywords: Felony disenfranchisement; International human rights law; Unreasonable restrictions; Discriminatory policies; Inter-American System for Protection of Human Rights.

Katia Silva Aragao, Maria de Fatima Borges, Evânia Altina Teixeira de Figueiredo, Danielly Bandeira Silveira, Elaine Cristina Maciel Porto, Sheyla Maria de Sousa Sa, Gisani de Souza Maia Teixeira, Anne Karolyne Gomes Brito, Carolline de Brito Lima, Lueline Paiva Elias. Pesquisa de Salmonella Spp em Lagosta (Panurilus Argus) Congelada A 18°C, por 24 Meses, Atraves de Metodo Rapido e Metodo Tradicional.. In: Anais do 12o Congresso Latinoamericano de Microbiologia e Higiene de Alimentos MICROAL 2014 [= Blucher Food Science Proceedings, num.1, vol.1]. Sao Paulo: Editora Blucher, 2014. DOI 10.5151/foodsci-microal-215 Pesquisa de Salmonella Spp em Lagosta (Panurilus argus) Congelada A -18°C, por 24 Meses, Atraves de Metodo Rapido e Metodo Tradicional.