Oxford open immunologyPub Date : 2022-06-27eCollection Date: 2022-01-01DOI: 10.1093/oxfimm/iqac004
P F McKay, J Zhou, R Frise, A K Blakney, C R Bouton, Z Wang, K Hu, K Samnuan, J C Brown, R Kugathasan, J Yeow, M M Stevens, W S Barclay, J S Tregoning, R J Shattock
{"title":"Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets.","authors":"P F McKay, J Zhou, R Frise, A K Blakney, C R Bouton, Z Wang, K Hu, K Samnuan, J C Brown, R Kugathasan, J Yeow, M M Stevens, W S Barclay, J S Tregoning, R J Shattock","doi":"10.1093/oxfimm/iqac004","DOIUrl":"https://doi.org/10.1093/oxfimm/iqac004","url":null,"abstract":"<p><p>COVID-19 has demonstrated the power of RNA vaccines as part of a pandemic response toolkit. Another virus with pandemic potential is influenza. Further development of RNA vaccines in advance of a future influenza pandemic will save time and lives. As RNA vaccines require formulation to enter cells and induce antigen expression, the aim of this study was to investigate the impact of a recently developed bioreducible cationic polymer, pABOL for the delivery of a self-amplifying RNA (saRNA) vaccine for seasonal influenza virus in mice and ferrets. Mice and ferrets were immunized with pABOL formulated saRNA vaccines expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime. Antibody responses, both binding and functional were measured in serum after immunization. Animals were then challenged with a matched influenza virus either directly by intranasal inoculation or in a contact transmission model. While highly immunogenic in mice, pABOL-formulated saRNA led to variable responses in ferrets. Animals that responded to the vaccine with higher levels of influenza virus-specific neutralizing antibodies were more protected against influenza virus infection. pABOL-formulated saRNA is immunogenic in ferrets, but further optimization of RNA vaccine formulation and constructs is required to increase the quality and quantity of the antibody response to the vaccine.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":" ","pages":"iqac004"},"PeriodicalIF":0.0,"publicationDate":"2022-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40419531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxford open immunologyPub Date : 2022-06-20eCollection Date: 2022-01-01DOI: 10.1093/oxfimm/iqac003
François Balloux, Cedric Tan, Leo Swadling, Damien Richard, Charlotte Jenner, Mala Maini, Lucy van Dorp
{"title":"The past, current and future epidemiological dynamic of SARS-CoV-2.","authors":"François Balloux, Cedric Tan, Leo Swadling, Damien Richard, Charlotte Jenner, Mala Maini, Lucy van Dorp","doi":"10.1093/oxfimm/iqac003","DOIUrl":"10.1093/oxfimm/iqac003","url":null,"abstract":"<p><p>SARS-CoV-2, the agent of the COVID-19 pandemic, emerged in late 2019 in China, and rapidly spread throughout the world to reach all continents. As the virus expanded in its novel human host, viral lineages diversified through the accumulation of around two mutations a month on average. Different viral lineages have replaced each other since the start of the pandemic, with the most successful Alpha, Delta and Omicron variants of concern (VoCs) sequentially sweeping through the world to reach high global prevalence. Neither Alpha nor Delta was characterized by strong immune escape, with their success coming mainly from their higher transmissibility. Omicron is far more prone to immune evasion and spread primarily due to its increased ability to (re-)infect hosts with prior immunity. As host immunity reaches high levels globally through vaccination and prior infection, the epidemic is expected to transition from a pandemic regime to an endemic one where seasonality and waning host immunization are anticipated to become the primary forces shaping future SARS-CoV-2 lineage dynamics. In this review, we consider a body of evidence on the origins, host tropism, epidemiology, genomic and immunogenetic evolution of SARS-CoV-2 including an assessment of other coronaviruses infecting humans. Considering what is known so far, we conclude by delineating scenarios for the future dynamic of SARS-CoV-2, ranging from the good-circulation of a fifth endemic 'common cold' coronavirus of potentially low virulence, the bad-a situation roughly comparable with seasonal flu, and the ugly-extensive diversification into serotypes with long-term high-level endemicity.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"3 1","pages":"iqac003"},"PeriodicalIF":0.0,"publicationDate":"2022-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long Covid brain fog: a neuroinflammation phenomenon?","authors":"Emma Kavanagh","doi":"10.1093/oxfimm/iqac007","DOIUrl":"https://doi.org/10.1093/oxfimm/iqac007","url":null,"abstract":"<p><p>Neuroinflammation is a process triggered by an attack on the immune system. Activation of microglia in response to an immune system challenge can lead to a significant impact on cognitive processes, such as learning, memory and emotional regulation. Long Covid is an ongoing problem, affecting an estimated 1.3 million people within the UK alone, and one of its more significant, and as yet unexplained, symptoms is brain fog. Here, we discuss the potential role of neuroinflammation in Long Covid cognitive difficulties. Inflammatory cytokines have been found to play a significant role in reductions in LTP and LTD, a reduction in neurogenesis, and in dendritic sprouting. The potential behavioural consequences of such impacts are discussed. It is hoped that this article will allow for greater examination of the effects of inflammatory factors on brain function, most particularly in terms of their role in chronic conditions.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"3 1","pages":"iqac007"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9358043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Is 'Long Covid' similar to 'Long SARS'?","authors":"John Patcai","doi":"10.1093/oxfimm/iqac002","DOIUrl":"https://doi.org/10.1093/oxfimm/iqac002","url":null,"abstract":"Is “Long Covid” similar to “Long SARS” (Severe Acute Respiratory Syndrome)? In 2019, a new pandemic started, and is still ongoing. The causative virus is the only known close relative of the SARS coronavirus (SARS-CoV-1), and is accordingly called SARS-CoV-2. Follow-up for between 2 and 10 years of 50 post SARS patients in a rehabilitation setting led to publications and clinical impressions that are summarized here regarding significant permanent disability for some of these patients. Similarities between permanent symptoms post SARS, and the reported so-far unresolving symptoms of Long Covid are remarkable. This makes it possible to predict that some Long Covid symptoms will be permanent.","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"3 1","pages":"iqac002"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9342392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Molecular mimicry among human proteinase 3 and bacterial antigens: implications for development of c-ANCA associated vasculitis.","authors":"","doi":"10.1093/oxfimm/iqac011","DOIUrl":"https://doi.org/10.1093/oxfimm/iqac011","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/oxfimm/iqac009.].</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"3 1","pages":"iqac011"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10795356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander T H Cocker, Emily M Whettlock, Brendan Browne, Pei F Lai, Jonathan K H Li, Sivatharjini P Sivarajasingam, Nesrina Imami, Mark R Johnson, Victoria Male
{"title":"Isolation of single cells from human uterus in the third trimester of pregnancy: myometrium, decidua, amnion and chorion.","authors":"Alexander T H Cocker, Emily M Whettlock, Brendan Browne, Pei F Lai, Jonathan K H Li, Sivatharjini P Sivarajasingam, Nesrina Imami, Mark R Johnson, Victoria Male","doi":"10.1093/oxfimm/iqac010","DOIUrl":"https://doi.org/10.1093/oxfimm/iqac010","url":null,"abstract":"<p><p>During pregnancy, interactions between uterine immune cells and cells of the surrounding reproductive tissues are thought to be vital for regulating labour. The mechanism that specifically initiates spontaneous labour has not been determined, but distinct changes in uterine immune cell populations and their activation status have been observed during labour at term gestation. To understand the regulation of human labour by the immune system, the ability to isolate both immune cells and non-immune cells from the uterus is required. Here, we describe protocols developed in our laboratory to isolate single cells from uterine tissues, which preserve both immune and non-immune cell populations for further analysis. We provide detailed methods for isolating immune and non-immune cells from human myometrium, chorion, amnion and decidua, together with representative flow cytometry analysis of isolated cell populations present. The protocols can be completed in tandem and take approximately 4-5 h, resulting in single-cell suspensions that contain viable leucocytes, and non-immune cells in sufficient numbers for single-cell analysis approaches such as flow cytometry and single cell RNA sequencing (scRNAseq).</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"3 1","pages":"iqac010"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9342394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lukoye Atwoli, Gregory E Erhabor, Aiah A Gbakima, Abraham Haileamlak, Jean-Marie Kayembe Ntumba, James Kigera, Laurie Laybourn-Langton, Bob Mash, Joy Muhia, Fhumulani Mavis Mulaudzi, David Ofori-Adjei, Friday Okonofua, Arash Rashidian, Maha El-Adawy, Siaka Sidibé, Abdelmadjid Snouber, James Tumwine, Mohammad Sahar Yassien, Paul Yonga, Lilia Zakhama, Chris Zielinski
{"title":"COP27 Climate Change Conference: urgent action needed for Africa and the world: Wealthy nations must step up support for Africa and vulnerable countries in addressing past, present and future impacts of climate change.","authors":"Lukoye Atwoli, Gregory E Erhabor, Aiah A Gbakima, Abraham Haileamlak, Jean-Marie Kayembe Ntumba, James Kigera, Laurie Laybourn-Langton, Bob Mash, Joy Muhia, Fhumulani Mavis Mulaudzi, David Ofori-Adjei, Friday Okonofua, Arash Rashidian, Maha El-Adawy, Siaka Sidibé, Abdelmadjid Snouber, James Tumwine, Mohammad Sahar Yassien, Paul Yonga, Lilia Zakhama, Chris Zielinski","doi":"10.1093/oxfimm/iqac008","DOIUrl":"https://doi.org/10.1093/oxfimm/iqac008","url":null,"abstract":"No abstract available.","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"3 1","pages":"iqac008"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10851755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Naive and memory T cells TCR-HLA-binding prediction.","authors":"Neta Glazer, Ofek Akerman, Yoram Louzoun","doi":"10.1093/oxfimm/iqac001","DOIUrl":"https://doi.org/10.1093/oxfimm/iqac001","url":null,"abstract":"<p><p>T cells recognize antigens through the interaction of their T cell receptor (TCR) with a peptide-major histocompatibility complex (pMHC) molecule. Following thymic-positive selection, TCRs in peripheral naive T cells are expected to bind MHC alleles of the host. Peripheral clonal selection is expected to further increase the frequency of antigen-specific TCRs that bind to the host MHC alleles. To check for a systematic preference for MHC-binding T cells in TCR repertoires, we developed Natural Language Processing-based methods to predict TCR<b>-</b>MHC binding independently of the peptide presented for Class I MHC alleles. We trained a classifier on published TCR<b>-</b>pMHC binding pairs and obtained a high area under curve (AUC) of over 0.90 on the test set. However, when applied to TCR repertoires, the accuracy of the classifier dropped. We thus developed a two-stage prediction model, based on large-scale naive and memory TCR repertoires, denoted T<b>C</b>R H<b>LA</b>-b<b>i</b>nding p<b>re</b>dictor (CLAIRE). Since each host carries multiple human leukocyte antigen (HLA) alleles, we first computed whether a TCR on a CD8 T cell binds an MHC from any of the host Class-I HLA alleles. We then performed an iteration, where we predict the binding with the most probable allele from the first round. We show that this classifier is more precise for memory than for naïve cells. Moreover, it can be transferred between datasets. Finally, we developed a CD4-CD8 T cell classifier to apply CLAIRE to unsorted bulk sequencing datasets and showed a high AUC of 0.96 and 0.90 on large datasets. CLAIRE is available through a GitHub at: https://github.com/louzounlab/CLAIRE, and as a server at: https://claire.math.biu.ac.il/Home.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"3 1","pages":"iqac001"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10851758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y Chavez, J Garces, R Díaz, M Escobar, A Sanchez, E Buendía, M Múnera
{"title":"Molecular mimicry among human proteinase 3 and bacterial antigens: implications for development of c-ANCA associated vasculitis.","authors":"Y Chavez, J Garces, R Díaz, M Escobar, A Sanchez, E Buendía, M Múnera","doi":"10.1093/oxfimm/iqac009","DOIUrl":"https://doi.org/10.1093/oxfimm/iqac009","url":null,"abstract":"<p><p>Wegener's granulomatosis is an autoimmune disease where autoantibodies target human autoantigen PR3, a serine protease locates on the neutrophil membrane. This disease affects blood small vessels and could be deadly. The origin of these autoantibodies is unknown, but infections have been implicated with autoimmune disease. In this study, we explored potential molecular mimicry between human PR3 and homologous pathogens through <i>in silico</i> analysis. Thirteen serine proteases from human pathogens (<i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Salmonella</i> sp., <i>Streptococcus suis</i>, <i>Vibrio parahaemolyticus</i>, <i>Bacteroides fragilis</i>, <i>Enterobacter ludwigii</i>, <i>Vibrio alginolyticus</i>, <i>Staphylococcus haemolyticus</i>, <i>Enterobacter cloacae</i>, <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>) shared structural homology and amino acid sequence identity with human PR3. Epitope prediction found an only conserved epitope IVGG, located between residues 59-74. However, multiple alignments showed conserved regions that could be involved in cross-reactivity between human and pathogens serine proteases (90-98, 101-108, 162-169, 267 and 262 residues positions). In conclusion, this is the first report providing <i>in silico</i> evidence about the existence of molecular mimicry between human and pathogens serine proteases, that could explain the origins of autoantibodies found in patients suffering from Wegener's granulomatosis.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"3 1","pages":"iqac009"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10851756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxford open immunologyPub Date : 2021-07-15eCollection Date: 2021-01-01DOI: 10.1093/oxfimm/iqab016
Amy S Codd, Stephanie J Hanna, Ewoud B Compeer, Felix C Richter, Eleanor J Pring, Ester Gea-Mallorquí, Mariana Borsa, Owen R Moon, D Oliver Scourfield, Awen M Gallimore, Anita Milicic
{"title":"Neutrophilia, lymphopenia and myeloid dysfunction: a living review of the quantitative changes to innate and adaptive immune cells which define COVID-19 pathology.","authors":"Amy S Codd, Stephanie J Hanna, Ewoud B Compeer, Felix C Richter, Eleanor J Pring, Ester Gea-Mallorquí, Mariana Borsa, Owen R Moon, D Oliver Scourfield, Awen M Gallimore, Anita Milicic","doi":"10.1093/oxfimm/iqab016","DOIUrl":"10.1093/oxfimm/iqab016","url":null,"abstract":"<p><p>Destabilization of balanced immune cell numbers and frequencies is a common feature of viral infections. This occurs due to, and further enhances, viral immune evasion and survival. Since the discovery of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which manifests in coronavirus disease 2019 (COVID-19), a great number of studies have described the association between this virus and pathologically increased or decreased immune cell counts. In this review, we consider the absolute and relative changes to innate and adaptive immune cell numbers, in COVID-19. In severe disease particularly, neutrophils are increased, which can lead to inflammation and tissue damage. Dysregulation of other granulocytes, basophils and eosinophils represents an unusual COVID-19 phenomenon. Contrastingly, the impact on the different types of monocytes leans more strongly to an altered phenotype, e.g. HLA-DR expression, rather than numerical changes. However, it is the adaptive immune response that bears the most profound impact of SARS-CoV-2 infection. T cell lymphopenia correlates with increased risk of intensive care unit admission and death; therefore, this parameter is particularly important for clinical decision-making. Mild and severe diseases differ in the rate of immune cell counts returning to normal levels post disease. Tracking the recovery trajectories of various immune cell counts may also have implications for long-term COVID-19 monitoring. This review represents a snapshot of our current knowledge, showing that much has been achieved in a short period of time. Alterations in counts of distinct immune cells represent an accessible metric to inform patient care decisions or predict disease outcomes.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"2 1","pages":"iqab016"},"PeriodicalIF":0.0,"publicationDate":"2021-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}