Immunization against severe acute respiratory syndrome Coronavirus 2: an overview

In the past years, numerous new fatal infections have emerged, including Ebola, Nipah, and Zika viruses, as well as coronaviruses. Recently, infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged in China, and were then transmitted all over the world, causing the coronavirus disease-19 (COVID-19) pandemic, which is transmitted at a higher rate than other diseases caused by coronaviruses. At the time of writing this review, COVID-19 is not contained in most countries in spite of quarantine, physical distancing, and enhanced hygiene measures. In this review, I address different methods for passive and active immunization against this virus, which is known to cause fatal respiratory disease, including natural passive immunization by breast milk, natural active immunization by herd immunization, artificial passive immunization by convalescent plasma or monoclonal antibodies, and artificial active immunization by vaccination. I hope this review will help design a prophylactic approach against outbreaks and pandemics of related coronaviruses in the future. Keywords: Breastfeeding; COVID-19; herd immunity; monoclonal antibodies; SARS-CoV; vaccine

Regulation of IRF-3-Dependent Innate Immune Signaling Pathway by the PLpro Domain of Non-Structural Protein 3 (NSP3) of Severe Acute Respiratory Syndrome (SARS) Coronavirus

The induction of Type I Interferons (IFNs) is a powerful and rapid innate defense mechanism against viral infection, and many viruses have developed elaborate strategies to overcome the antiviral effects of IFN, ensuring their survival and replication. Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic virus that causes severe lung disease in humans and is associated with high mortality rates. SARS-CoV, like all other successful viruses, encode proteins that counteract the innate immune response. A number of reports have indicated the papain-like protease (PLpro) domain of SARS-CoV Non-Structural Protein 3 (NSP3) as a powerful interferon antagonist, by suppressing interferon regulatory factor 3 (IRF3) dependent innate antiviral defenses. IRF3 plays a key role in viral-induced type I IFN induction pathway. Thus, viruses are well-known to evade the establishment of an antiviral state by regulating the activation of IRF3. However, functional studies detailing the PLpro IFN antagonistic abilities, are not describe in the context of the full length nsp3 protein, in which it is contained in virus infected cells. Nsp3 is the largest replicase gene product in the coronavirus genome, which contains several functional domains that are required for coronavirus replication. Establishment of a stable and controllable CoV-nsp3 expression system will allow the physiological relevant study of the PLpro mediated function of this protein. Here, I described the development of tetracycline-inducible mammalian cell lines for stable expression of the full length nsp3 of HCoV-OC43, HCoV-NL63, MERS-CoV, and SARS-CoV, respectively. Although these cell lines exhibited stable and tight control of nsp3 expression in the presence of tetracycline, I observed a variation in CoV’s nsp3 protein expression levels. However, HeLa-Fit-SCoV-nsp3 and HeLa-Fit-SCoV-nsp3-delPLP stable cell lines expressed SARS-nsp3 and SARS-nsp3-delPLP robustly and at comparable levels. I found that expression of SARS-CoV nsp3 compromised virus-induced expression of IRF-3-dependent antiviral genes and that such ability depended on the PLpro domain. In agreement with our previous study examining the effects of the PLpro domain, the inhibitory effect was downstream of the IRF-3 kinases while upstream of IRF-3. Overall, my data demonstrates that SARS-CoV nsp3 is a bona fide interferon antagonist, which acts through PLpro-mediated suppression of IRF-3 activation

Public sector pricing policies : a review of Bank policy and practice

Nearly a decade has passed since the Bank codified its position on cost recovery policies (OMS 2.25) for public sector projects. In a review of 13 sectors, the authors find that the Bank guidelines are followed fairly closely in seven sectors: coal, irrigation, oil/gas, power, roads, telecommunications, and water/sewerage. In the other six sectors the focus is heavily on either distributional (health, education, housing) or financial (fertilizer, ports, railways) concerns - with little attempt to incorporate economic pricing principles. Efficiency pricing is not irrelevant or impossible in these sectors, and - even if used only as a benchmark - could improve sector management and project selection and design.Environmental Economics&Policies,Economic Theory&Research,Health Monitoring&Evaluation,Public Sector Economics&Finance,Banks&Banking Reform

COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective. Co-authors include: Anna Niarakis, Alexander Mazein, Inna Kuperstein, Robert Phair, Aurelio Orta-Resendiz, Vidisha Singh, Sara Sadat Aghamiri, Marcio Luis Acencio, Enrico Glaab, Andreas Ruepp, Gisela Fobo, Corinna Montrone, Barbara Brauner, Goar Frishman, Luis Cristóbal Monraz Gómez, Julia Somers, Matti Hoch, Shailendra Kumar Gupta, Julia Scheel, Hanna Borlinghaus, Tobias Czauderna, Falk Schreiber, Arnau Montagud, Miguel Ponce de Leon, Akira Funahashi, Yusuke Hiki, Noriko Hiroi, Takahiro G Yamada, Andreas Dräger, Alina Renz, Muhammad Naveez, Zsolt Bocskei, FrancescoMessina, Daniela Börnigen, Liam Fergusson, Marta Conti, Marius Rameil, Vanessa Nakonecnij, Jakob Vanhoefer, Leonard Schmiester, Muying Wang, Emily E Ackerman, Jason E Shoemaker, Jeremy Zucker, Kristie Oxford, Jeremy Teuton, Ebru Kocakaya, Gökçe Yağmur Summak, Kristina Hanspers, Martina Kutmon, Susan Coort, Lars Eijssen, Friederike Ehrhart, Devasahayam Arokia Balaya Rex, Denise Slenter, Marvin Martens, Nhung Pham, Robin Haw, Bijay Jassal, Lisa Matthews, Marija Orlic-Milacic, Andrea Senff-Ribeiro, Karen Rothfels, Veronica Shamovsky, Ralf Stephan, Cristoffer Sevilla, Thawfeek Varusai, Jean-Marie Ravel, Rupsha Fraser, Vera Ortseifen, Silvia Marchesi, Piotr Gawron, Ewa Smula, Laurent Heirendt, Venkata Satagopam, Guanming Wu, Anders Riutta, Martin Golebiewski, Stuart Owen, Carole Goble, Xiaoming Hu, Rupert W Overall, Dieter Maier, Angela Bauch, Benjamin M Gyori, John A Bachman, Carlos Vega, Valentin Grouès, Miguel Vazquez, Pablo Porras, Luana Licata, Marta Iannuccelli, Francesca Sacco, Anastasia Nesterova, Anton Yuryev, Anita de Waard, Denes Turei, Augustin Luna, Ozgun Babur, Sylvain Soliman, Alberto Valdeolivas, Marina Esteban-Medina, Maria Peña-Chilet, Kinza Rian, Tomáš Helikar, Bhanwar Lal Puniya, Dezso Modos, Agatha Treveil, Marton Olbei, Bertrand De Meulder, Stephane Ballereau, Aurélien Dugourd, Aurélien Naldi, Vincent Noël, Laurence Calzone, Chris Sander, Emek Demir, Tamas Korcsmaros, Tom C Freeman, Franck Augé, Jacques S Beckmann, Jan Hasenauer, Olaf Wolkenhauer, Egon L Willighagen, Alexander R Pico, Chris T Evelo, Marc E Gillespie, Lincoln D Stein, Henning Hermjakob, Peter D’Eustachio, Julio Saez-Rodriguez, Joaquin Dopazo, Alfonso Valencia, Hiroaki Kitano, Emmanuel Barillot, Charles Auffray, Rudi Balling, Reinhard Schneide

Comparison of two immunoassays for detection of anti-SARS cov-2 antibodies among healthcare workers at a tertiary referral Hospital in Nairobi, Kenya

Background: Tests for antibodies against severe acute respiratory syndrome coronavirus 2, the aetiologic agent of coronavirus disease 2019, provide evidence of past infection or immunization. At the individual level, they are useful as markers of protection against severe disease and in cases where the diagnosis by nucleic acid amplification is inconclusive. At the population level, they are an indirect measure of exposure and may be useful in monitoring changes in viral infection or uptake of immunization over time. The interpretation and optimal use of antibody assays on populations requires an appreciation of the wide variability in individual antibody responses, the timing of testing, and individual assay performance. Direct comparison of assays in representative populations is one way of providing information that will aid in optimization of their use. Objectives: The primary objective in this pre-vaccine study was to determine the difference in estimates of prevalence of anti-SARS-CoV-2 antibodies in a population of health care workers tested using two qualitative immunoassay platforms targeting two different SARS-CoV-2 proteins. Secondary objectives were: (i) to determine the proportion of discordant results, (ii) to investigate sex, age, and time since exposure as predictors of discordance, and (iii) describe the changes in antibody level with time for each assay. Methods: This was a secondary analysis of data collected from an earlier cross-sectional study that determined seroprevalence of antibodies against nucleocapsid and spike proteins of SARSCoV-2 in sera collected from the study population. Antibodies against SARS-CoV-2 were detected using two different assays detecting anti-nucleocapsid and anti-spike antibodies in samples collected at a single time point for each participant. The proportion with a positive result by each assay was determined, as was the proportion of discordant results. Age, sex, and time as predictors of discordance were explored using a binomial logistic regression model. Plots of antibody index against time were prepared for each assay. Results:A total of 1477 serum samples from 643 (43.5%) males and 834 females were analysed. This study found a prevalence of 18.3% (95% CI, 16.4% – 20.3%) and 26.5% (95% CI, 24.2% – 28.7%), respectively, of antibodies against nucleocapsid and spike. Overall, 162 (10.9%) participants had discordant antibody results. Of the 107 individuals with a prior PCR positive result, discordance was found in 27 (25.2%). Discordance was found to increase with v time since positive PCR; 100% of results of samples collected at 28 weeks post PCR were discordant. One hundred forty-one (87.1%) of participants with discordant results had a positive spike result and negative nucleocapsid result; this figure was 74.1% in those with a prior positive PCR result. Age (OR = 0.94, 95% CI 0.89 – 1.00, P Conclusion: Following natural infection by SARS-CoV-2, the seroprevalence of anti-spike antibodies is higher than that of anti-nucleocapsid antibodies in a population naïve to the SARS CoV-2 vaccine. Discordance in antibody result is more likely the longer the interval between exposure and testing. Antibodies against spike remain detectable for a longer duration than those against nucleocapsid. Assays detecting anti-spike antibodies would result in higher estimates of seroprevalence in surveillance studies