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The emergence of SARS-CoV-2 has meant that pandemic preparedness has become a major focus of the global scientific community. Gathered in the historic St Edmund Hall college in Oxford, the one-day LPMHealthcare conference on emerging viruses (6 September 2023) sought to review and learn from past pandemics-the current SARS-CoV-2 pandemic and the Mpox outbreak-and then look towards potential future pandemics. This includes an emphasis on monitoring the "traditional" reservoirs of viruses with zoonotic potential, as well as possible new sources of spillover events, e.g., bats, which we are coming into closer contact with due to climate change and the impacts of human activities on habitats. Continued vigilance and investment into creative scientific solutions is required for issues including the long-term physical and psychological effects of COVID-19, i.e., long COVID. The evaluation of current systems, including environmental monitoring, communication (with the public, regulatory authorities, and governments), and training; assessment of the effectiveness of the technologies/assays we have in place currently; and lobbying of the government and the public to work with scientists are all required in order to build trust moving forward. Overall, the SARS-CoV-2 pandemic has shown how many sectors can work together to achieve a global impact in times of crisis.
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BACKGROUND: The beneficial properties of wine by-products include actions that help prevent and treat cardiovascular conditions such as hypertension, primarily due to their antioxidant effects. Novel pharmacotherapies are being developed to treat arterial hypertension, including investigations into natural products exhibiting biological activity, necessitating rigorous evaluation of their efficacy and safety. This study aimed to identify and quantify phenolic compounds in Syrah (Vitis vinifera) grapes grown in the Brazilian Cerrado and their presence in winemaking by-products. It also examined the effects of grape pomace on blood pressure. METHODS: Fresh grapes, pomace, and lees, were subjected to spectrophotometric determination of total phenolic compounds, followed by identification and quantification using HPLC-DAD-ESI-MSn. Normotensive male rats (Wistar) and spontaneously hypertensive rats (SHR) received grape pomace-enriched (150 or 300 mg/kg/day, 14 days) or standard chow. Indirect arterial pressure was assessed, while vascular reactivity was evaluated in mesenteric resistance arteries. RESULTS: Pomace samples exhibited higher total phenolic compound concentrations than grapes or lees. Seven derivatives of hydroxycinnamic acids and twenty-one flavonols were identified. Quercetin-3-glucoside and ethyl caffeate were the most abundant phenolic compounds. Grape pomace-enriched chow demonstrated a dose-dependent hypotensive effect in rats. CONCLUSION: the abundance of flavonols and hydroxycinnamic acids, combined with their hypotensive effects, underscores the therapeutic potential of fine wine-making by-products produced in the Brazilian Cerrado.
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Antihipertensivos , Presión Sanguínea , Hipertensión , Fenoles , Ratas Endogámicas SHR , Ratas Wistar , Vitis , Vino , Animales , Vitis/química , Masculino , Fenoles/análisis , Fenoles/farmacología , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Ratas , Vino/análisis , Antihipertensivos/farmacología , Antioxidantes/farmacología , Antioxidantes/análisis , Extractos Vegetales/farmacología , Frutas/química , BrasilRESUMEN
BACKGROUND AND AIMS: HBV and HIV coinfection is a common occurrence globally, with significant morbidity and mortality. Both viruses lead to immune dysregulation including changes in natural killer (NK) cells, a key component of antiviral defense and a promising target for HBV cure strategies. Here we used high-throughput single-cell analysis to explore the immune cell landscape in people with HBV mono-infection and HIV/HBV coinfection, on antiviral therapy, with emphasis on identifying the distinctive characteristics of NK cell subsets that can be therapeutically harnessed. APPROACH AND RESULTS: Our data show striking differences in the transcriptional programs of NK cells. HIV/HBV coinfection was characterized by an over-representation of adaptive, KLRC2 -expressing NK cells, including a higher abundance of a chemokine-enriched ( CCL3/CCL4 ) adaptive cluster. The NK cell remodeling in HIV/HBV coinfection was reflected in enriched activation pathways, including CD3ζ phosphorylation and ZAP-70 translocation that can mediate stronger antibody-dependent cellular cytotoxicity responses and a bias toward chemokine/cytokine signaling. By contrast, HBV mono-infection imposed a stronger cytotoxic profile on NK cells and a more prominent signature of "exhaustion" with higher circulating levels of HBsAg. Phenotypic alterations in the NK cell pool in coinfection were consistent with increased "adaptiveness" and better capacity for antibody-dependent cellular cytotoxicity compared to HBV mono-infection. Overall, an adaptive NK cell signature correlated inversely with circulating levels of HBsAg and HBV-RNA in our cohort. CONCLUSIONS: This study provides new insights into the differential signature and functional profile of NK cells in HBV and HIV/HBV coinfection, highlighting pathways that can be manipulated to tailor NK cell-focused approaches to advance HBV cure strategies in different patient groups.
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Citotoxicidad Celular Dependiente de Anticuerpos , Coinfección , Infecciones por VIH , Células Asesinas Naturales , Humanos , Infecciones por VIH/inmunología , Infecciones por VIH/complicaciones , Células Asesinas Naturales/inmunología , Coinfección/inmunología , Masculino , Femenino , Adulto , Hepatitis B/inmunología , Hepatitis B/complicaciones , Persona de Mediana Edad , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virologíaRESUMEN
Avian A(H5N1) influenza virus poses an elevated zoonotic threat to humans, and no pharmacological products are currently registered for fast-acting pre-exposure protection in case of spillover leading to a pandemic. Here, we show that an epitope on the stem domain of H5 hemagglutinin is highly conserved and that the human monoclonal antibody CR9114, targeting that epitope, potently neutralizes all pseudotyped H5 viruses tested, even in the rare case of substitutions in its epitope. Further, intranasal administration of CR9114 fully protects mice against A(H5N1) infection at low dosages, irrespective of pre-existing immunity conferred by the quadrivalent seasonal influenza vaccine. These data provide a proof-of-concept for broad, pre-exposure protection against a potential future pandemic using the intranasal administration route. Studies in humans should assess if autonomous administration of a broadly-neutralizing monoclonal antibody is safe and effective and can thus contribute to pandemic preparedness.
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Subtipo H5N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Animales , Ratones , Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Administración Intranasal , Anticuerpos Antivirales , Epítopos , Glicoproteínas Hemaglutininas del Virus de la Influenza , Ratones Endogámicos BALB CRESUMEN
Introduction: The Eidolon helvum fruit bat is one of the most widely distributed fruit bats in Africa and known to be a reservoir for several pathogenic viruses that can cause disease in animals and humans. To assess the risk of zoonotic spillover, we conducted a serological survey of 304 serum samples from E. helvum bats that were captured for human consumption in Makurdi, Nigeria. Methods: Using pseudotyped viruses, we screened 304 serum samples for neutralizing antibodies against viruses from the Coronaviridae, Filoviridae, Orthomyxoviridae and Paramyxoviridae families. Results: We report the presence of neutralizing antibodies against henipavirus lineage GH-M74a virus (odds ratio 6.23; p < 0.001), Nipah virus (odds ratio 4.04; p = 0.00031), bat influenza H17N10 virus (odds ratio 7.25; p < 0.001) and no significant association with Ebola virus (odds ratio 0.56; p = 0.375) in this bat cohort. Conclusion: The data suggest a potential risk of zoonotic spillover including the possible circulation of highly pathogenic viruses in E. helvum populations. These findings highlight the importance of maintaining sero-surveillance of E. helvum, and the necessity for further, more comprehensive investigations to monitor changes in virus prevalence, distribution over time, and across different geographic locations.
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Quirópteros , Virosis , Animales , Humanos , Nigeria/epidemiología , Zoonosis/epidemiología , Anticuerpos NeutralizantesRESUMEN
Natural killer (NK) cell subsets with adaptive properties are emerging as regulators of vaccine-induced T and B cell responses and are specialized towards antibody-dependent functions contributing to SARS-CoV-2 control. Although HIV-1 infection is known to affect the NK cell pool, the additional impact of SARS-CoV-2 infection and/or vaccination on NK cell responses in people living with HIV (PLWH) has remained unexplored. Our data show that SARS-CoV-2 infection skews NK cells towards a more differentiated/adaptive CD57+FcεRIγ- phenotype in PLWH. A similar subset was induced following vaccination in SARS-CoV-2 naïve PLWH in addition to a CD56bright population with cytotoxic potential. Antibody-dependent NK cell function showed robust and durable responses to Spike up to 148 days post-infection, with responses enriched in adaptive NK cells. NK cell responses were further boosted by the first vaccine dose in SARS-CoV-2 exposed individuals and peaked after the second dose in SARS-CoV-2 naïve PLWH. The presence of adaptive NK cells associated with the magnitude of cellular and humoral responses. These data suggest that features of adaptive NK cells can be effectively engaged to complement and boost vaccine-induced adaptive immunity in potentially more vulnerable groups such as PLWH.
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COVID-19 , Infecciones por VIH , VIH-1 , Vacunas , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Vacunación , Células Asesinas Naturales , Anticuerpos , Infecciones por VIH/complicaciones , Anticuerpos AntiviralesRESUMEN
Introduction: the COVID-19 pandemic has increased the number of hospitalizations and is responsible for increasing the workload of nursing professionals with a deficiency in human resources and personal protective equipment.Objective: to analyze aspects related to the working conditions of Nursing professionals in the context of COVID-19.Methods: documentary research recorded under narratives in the databases of the Federal Nursing Council, the Regional Nursing Councils of Espírito Santo and Pernambuco, the Federal Public University and Social Media.Results: are presented and analyzed according to the categories: a) nursing work conditions, threatening the worker's health and life; b) the autonomy of nurses in the full exercise of their profession and the cultural aspect of the dominant ideology; c) the Federal Nursing Council and the Regional Nursing Councils of Espírito Santo and Pernambuco as disciplining, normalizing, managing and controlling bodies for the professional practice of nursing.Conclusion: the narratives found in this study demonstrate the precarious working conditions, exacerbated by the pandemic, and the role of nursing in coping with COVID-19
Introdução: a pandemia pela COVID-19 tem elevado o número de internações hospitalares sendo responsável pelo aumento da carga de trabalho dos profissionais de enfermagem com deficiência de recursos humanos e de equipamentos de proteção individual. Objetivo: analisar aspectos relativos às condições de trabalho dos profissionais da Enfermagem no contexto da COVID-19. Método: pesquisa documental registrada sob narrativas nas bases de dados do Conselho Federal de Enfermagem, dos Conselhos Regionais de Enfermagem do Espírito Santo e de Pernambuco, de Universidade Pública Federal e das Mídias Sociais. Resultados: são apresentados e analisados mediante as categorias: a) as condições de trabalho da enfermagem, ameaçando a saúde e vida do trabalhador; b) a autonomia do enfermeiro/a no exercício pleno de sua profissão e aspecto cultural da ideologia dominante; c) o Conselho Federal de Enfermagem e os Conselhos Regionais de Enfermagem do Espírito Santo e de Pernambuco como órgãos disciplinadores, normalizadores, gestores e de controle do exercício profissional da enfermagem. Conclusão: as narrativas encontradas nesse estudo demonstraram as precárias condições de trabalho, agudizadas pela pandemia, e o protagonismo da enfermagem no enfrentamento da COVID-19.
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This paper aimed to analyze the reduction in the ballast layer permeability simulated in a laboratory in saturated conditions by the presence of rock dust as a contaminant of three types of rocks explored in different deposits in the northern region of the state of Rio de Janeiro, Brazil, through laboratory testing relating the physical properties of rock particles before and after sodium sulfate attack. Sodium sulfate attack is justified by the proximity of some sections of the planned EF-118 Vitória-Rio railway line to the coast and of the sulfated water table to the ballast bed, which could degrade the material used and compromise the railway track. Granulometry and permeability tests were performed to compare ballast samples with fouling rates of 0, 10, 20, and 40% rock dust by volume. A constant head permeameter was used to analyze hydraulic conductivity and establish correlations between the petrography and mercury intrusion porosimetry of the rocks, namely two types of metagranite (Mg1 and Mg3) and a gneisse (Gn2). Rocks, such as Mg1 and Mg3, with a larger composition of minerals susceptible to weathering according to petrography analyses, tend to be more sensitive to weathering tests. This, in conjunction with the climate in the region studied, with average annual temperature and rainfall of 27 °C and 1200 mm, could compromise track safety and user comfort. Additionally, the Mg1 and Mg3 samples showed greater percentage variation in wear after the Micro-Deval test, which could damage the ballast due to the considerable changeability of the material. The mass loss caused by abrasion due to the passage of rail vehicles was assessed by the Micro-Deval test, with Mg3 (intact rock) declining from 8.50 ± 1.5 to 11.04 ± 0.5% after chemical attack. However, Gn2, which exhibited the greatest mass loss among the samples, showed no significant variation in average wear, and its mineralogical characteristics remained almost unchanged after 60 sodium sulfate cycles. These aspects, combined with its satisfactory hydraulic conductivity rate, indicate that Gn2 is suitable for use as railway ballast in the EF-118 railway line.
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SARS-CoV-2 continues to circulate in the human population necessitating regular booster immunization for its long-term control. Ideally, vaccines should ideally not only protect against symptomatic disease, but also prevent transmission via asymptomatic shedding and cover existing and future variants of the virus. This may ultimately only be possible through induction of potent and long-lasting immune responses in the nasopharyngeal tract, the initial entry site of SARS-CoV-2. To this end, we have designed a vaccine based on recombinantly expressed receptor binding domain (RBD) of SARS-CoV-2, fused to the C-terminus of C. perfringens enterotoxin, which is known to target Claudin-4, a matrix molecule highly expressed on mucosal microfold (M) cells of the nasal and bronchial-associated lymphoid tissues. To further enhance immune responses, the vaccine was adjuvanted with a novel toll-like receptor 3/RIG-I agonist (Riboxxim™), consisting of synthetic short double stranded RNA. Intranasal prime-boost immunization of mice induced robust mucosal and systemic anti-SARS-CoV-2 neutralizing antibody responses against SARS-CoV-2 strains Wuhan-Hu-1, and several variants (B.1.351/beta, B.1.1.7/alpha, B.1.617.2/delta), as well as systemic T-cell responses. A combination vaccine with M-cell targeted recombinant HA1 from an H1N1 G4 influenza strain also induced mucosal and systemic antibodies against influenza. Taken together, the data show that development of an intranasal SARS-CoV-2 vaccine based on recombinant RBD adjuvanted with a TLR3 agonist is feasible, also as a combination vaccine against influenza.
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Vacunas contra la COVID-19 , COVID-19 , Gripe Humana , Animales , Humanos , Ratones , Adyuvantes Inmunológicos , Adyuvantes Farmacéuticos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Clostridium perfringens , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Mucosa Gástrica , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Células M , SARS-CoV-2 , Receptor Toll-Like 3RESUMEN
We have developed an influenza hemagglutinin (HA) pseudotype (PV) library encompassing all influenza A (IAV) subtypes from HA1-HA18, influenza B (IBV) subtypes (both lineages), representative influenza C (ICV), and influenza D (IDV) viruses. These influenza HA (or hemagglutinin-esterase fusion (HEF) for ICV and IDV) pseudotypes have been used in a pseudotype microneutralization assay (pMN), an optimized luciferase reporter assay, that is highly sensitive and specific for detecting neutralizing antibodies against influenza viruses. This has been an invaluable tool in detecting the humoral immune response against specific hemagglutinin or hemagglutinin-esterase fusion proteins for IAV to IDV in serum samples and for screening antibodies for their neutralizing abilities. Additionally, we have also produced influenza neuraminidase (NA) pseudotypes for IAV N1-N9 subtypes and IBV lineages. We have utilized these NA-PV as surrogate antigens in in vitro assays to assess vaccine immunogenicity. These NA PV have been employed as the source of neuraminidase enzyme activity in a pseudotype enzyme-linked lectin assay (pELLA) that is able to measure neuraminidase inhibition (NI) titers of reference antisera, monoclonal antibodies, and postvaccination sera. Here we show the production of influenza HA, HEF, and NA PV and their employment as substitutes for wild-type viruses in influenza serological and neutralization assays. We also introduce AutoPlate, an easily accessible web app that can analyze data from pMN and pELLA quickly and efficiently, plotting inhibition curves and calculating half-maximal concentration (IC50) neutralizing antibody titers. These serological techniques coupled with user-friendly analysis tools are faster, safer, inexpensive alternatives to classical influenza assays while also offering the reliability and reproducibility to advance influenza research and make it more accessible to laboratories around the world.
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Vacunas contra la Influenza , Gripe Humana , Humanos , Reproducibilidad de los Resultados , Anticuerpos Antivirales , Hemaglutininas , Neuraminidasa/genética , Pseudotipado Viral , Esterasas , Glicoproteínas Hemaglutininas del Virus de la Influenza/genéticaRESUMEN
To better understand how inhibition of the influenza neuraminidase (NA) protein contributes to protection against influenza, we produced lentiviral vectors pseudotyped with an avian H11 hemagglutinin (HA) and the NA of all influenza A (N1-N9) subtypes and influenza B (B/Victoria and B/Yamagata). These NA viral pseudotypes (PV) possess stable NA activity and can be utilized as target antigens in in vitro assays to assess vaccine immunogenicity. Employing these NA PV, we developed an enzyme-linked lectin assay (pELLA) for routine serology to measure neuraminidase inhibition (NI) titers of reference antisera, monoclonal antibodies and post-vaccination sera with various influenza antigens. We also show that the pELLA is more sensitive than the commercially available NA-Fluor™ in detecting NA inhibition in these samples. Our studies may lead to establishing the protective NA titer that contributes to NA-based immunity. This will aid in the design of superior, longer lasting and more broadly protective vaccines that can be employed together with HA-targeted vaccines in a pre-pandemic approach.
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OBJECTIVES: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. METHODS: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. RESULTS: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40). CONCLUSIONS: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. TRIAL REGISTRATION NUMBER: ISRCTN11041050.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , COVID-19/prevención & control , Estudios de Casos y Controles , Humanos , Reinfección/prevención & control , VacunaciónRESUMEN
Current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines, based on the ancestral Wuhan strain, were developed rapidly to meet the needs of a devastating global pandemic. People living with Human Immunodeficiency Virus (PLWH) have been designated as a priority group for SARS-CoV-2 vaccination in most regions and varying primary courses (two- or three-dose schedule) and additional boosters are recommended depending on current CD4+ T cell count and/or detectable HIV viraemia. From the current published data, licensed vaccines are safe for PLWH, and stimulate robust responses to vaccination in those well controlled on antiretroviral therapy and with high CD4+ T cell counts. Data on vaccine efficacy and immunogenicity remain, however, scarce in PLWH, especially in people with advanced disease. A greater concern is a potentially diminished immune response to the primary course and subsequent boosters, as well as an attenuated magnitude and durability of protective immune responses. A detailed understanding of the breadth and durability of humoral and T cell responses to vaccination, and the boosting effects of natural immunity to SARS-CoV-2, in more diverse populations of PLWH with a spectrum of HIV-related immunosuppression is therefore critical. This article summarizes focused studies of humoral and cellular responses to SARS-CoV-2 infection in PLWH and provides a comprehensive review of the emerging literature on SARS-CoV-2 vaccine responses. Emphasis is placed on the potential effect of HIV-related factors and presence of co-morbidities modulating responses to SARS-CoV-2 vaccination, and the remaining challenges informing the optimal vaccination strategy to elicit enduring responses against existing and emerging variants in PLWH.
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We developed an influenza hemagglutinin (HA) pseudotype library encompassing Influenza A subtypes HA1-18 and Influenza B subtypes (both lineages) to be employed in influenza pseudotype microneutralization (pMN) assays. The pMN is highly sensitive and specific for detecting virus-specific neutralizing antibodies against influenza viruses and can be used to assess antibody functionality in vitro. Here we show the production of these viral HA pseudotypes and their employment as substitutes for wildtype viruses in influenza neutralization assays. We demonstrate their utility in detecting serum responses to vaccination with the ability to evaluate cross-subtype neutralizing responses elicited by specific vaccinating antigens. Our findings may inform further preclinical studies involving immunization dosing regimens in mice and may help in the creation and selection of better antigens for vaccine design. These HA pseudotypes can be harnessed to meet strategic objectives that contribute to the strengthening of global influenza surveillance, expansion of seasonal influenza prevention and control policies, and strengthening pandemic preparedness and response.
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Influenza B viruses (IBV) cause respiratory disease epidemics in humans and are therefore components of seasonal influenza vaccines. Serological methods are employed to evaluate vaccine immunogenicity prior to licensure. However, classical methods to assess influenza vaccine immunogenicity such as the hemagglutination inhibition assay (HI) and the serial radial hemolysis assay (SRH), have been proven to have many limitations. As such, there is a need to develop innovative methods that can improve on these traditional assays and provide advantages such as ease of production and access, safety, reproducibility, and specificity. It has been previously demonstrated that the use of replication-defective viruses, such as lentiviral vectors pseudotyped with influenza A hemagglutinins in microneutralization assays (pMN) is a safe and sensitive alternative to study antibody responses elicited by natural influenza infection or vaccination. Consequently, we have produced Influenza B hemagglutinin-pseudotypes (IBV PV) using plasmid-directed transfection. To activate influenza B hemagglutinin, we have explored the use of proteases in increasing PV titers via their co-transfection during pseudotype virus production. When tested for their ability to transduce target cells, the influenza B pseudotypes produced exhibit tropism for different cell lines. The pseudotypes were evaluated as alternatives to live virus in microneutralization assays using reference sera standards, mouse and human sera collected during vaccine immunogenicity studies, surveillance sera from seals, and monoclonal antibodies (mAbs) against IBV. The influenza B pseudotype pMN was found to effectively detect neutralizing and cross-reactive responses in all assays and shows promise as an effective and versatile tool in influenza research.
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Anticuerpos Monoclonales/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Inmunogenicidad Vacunal/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/inmunología , Lentivirus/inmunología , Células A549 , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Especificidad de Anticuerpos/inmunología , Perros , Vectores Genéticos/genética , Vectores Genéticos/inmunología , Células HEK293 , Glicoproteínas Hemaglutininas del Virus de la Influenza/clasificación , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Virus de la Influenza B/genética , Virus de la Influenza B/fisiología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , Lentivirus/genética , Células de Riñón Canino Madin Darby , Pruebas de Neutralización/métodos , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/virología , Vacunación , Potencia de la VacunaRESUMEN
The emergence of COVID-19 has emphasised that biological assay data must be analysed quickly to develop safe, effective and timely vaccines/therapeutics. For viruses such as SARS-CoV-2, the primary way of measuring immune correlates of protection is through assays such as the pseudotype microneutralisation (pMN) assay, thanks to its safety and versatility. However, despite the presence of existing tools for data analysis such as PRISM and R the analysis of these assays remains cumbersome and time-consuming. We introduce an open-source R Shiny web application and R library (AutoPlate) to accelerate data analysis of dose-response curve immunoassays. Using example data from influenza studies, we show that AutoPlate improves on available analysis software in terms of ease of use, flexibility and speed. AutoPlate (https://philpalmer.shinyapps.io/AutoPlate/) is a tool for the use of laboratories and wider scientific community to accelerate the analysis of biological assays in the development of viral vaccines and therapeutics.
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COVID-19/diagnóstico , Inmunoensayo/estadística & datos numéricos , Virus de la Influenza A/fisiología , Gripe Humana/diagnóstico , SARS-CoV-2/fisiología , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/metabolismo , Interpretación Estadística de Datos , Relación Dosis-Respuesta a Droga , Humanos , Inmunoensayo/normas , Control de Calidad , Programas InformáticosRESUMEN
Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda), and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.
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Vacunas contra el SIDA/inmunología , Antiinfecciosos/inmunología , Diseño de Fármacos , Animales , Formación de Anticuerpos/inmunología , Ensayos Clínicos como Asunto , HumanosRESUMEN
EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur) involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training. EUROPRISE held its second annual conference in Budapest in November, 2009. The conference had 143 participants and their presentations covered aspects of vaccine and microbicide research, development and discovery. Since training is a major task of the Network, the students of the EUROPRISE PhD program summarized certain presentations and their view of the conference in this paper.