LitCovid-sentences  

PMC:7200337 / 103489-113370 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T621 0-19 Sentence denotes Vaccine Development
T622 20-281 Sentence denotes The devastating effects of the pandemic spread of SARS-CoV-2 in a globally naive population has resulted in unprecedented efforts to rapidly develop, test, and disseminate a vaccine to protect against COVID-19 or to mitigate the effects of SARS-CoV-2 infection.
T623 282-463 Sentence denotes Although vaccination has a long and successful history as an effective global health strategy, there are currently no approved vaccines to protect humans against CoVs (André, 2003).
T624 464-672 Sentence denotes Previous work after the SARS-CoV-1 and MERS-CoV epidemics has provided a foundation on which many current efforts are currently building upon, including the importance of the S protein as a potential vaccine.
T625 673-861 Sentence denotes Diverse vaccine platforms and preclinical animal models have been adapted to SARS-CoV-2, facilitating fast-moving and robust progress in creating and testing SARS-CoV-2 vaccine candidates.
T626 862-998 Sentence denotes A number of vaccine candidates are already being tested in clinical trials, and more are continuing to progress toward clinical testing.
T627 1000-1033 Sentence denotes The S Protein as a Vaccine Target
T628 1034-1183 Sentence denotes Since SARS-CoV-1 first emerged, the S protein has been favored as the most promising target for vaccine development to protect against CoV infection.
T629 1184-1495 Sentence denotes This particular viral protein has important roles in viral entry and in stimulating the immune response during natural infection and in vaccination studies of both SARS-CoV-1 and MERS-CoV (Du et al., 2009, Song et al., 2019, Zhou et al., 2018), which has also been confirmed for SARS-CoV-2 (Walls et al., 2020).
T630 1496-1669 Sentence denotes The S protein has been found to induce robust and protective humoral and cellular immunity, including the development of nAbs and T cell-mediated immunity (Du et al., 2009).
T631 1670-2143 Sentence denotes In animal models, correlates of protection against SARS-CoV-1 infection appear to be induction of nAbs against the S protein, although antibodies to other proteins have been detected, such as those against nucleoprotein (N) and ORF3a (Qiu et al., 2005, Sui et al., 2005). nAbs are also believed to protect against infection by blocking receptor binding and viral entry, which has been shown with pseudovirus-based neutralization assays (Ni et al., 2020, Nie et al., 2020a).
T632 2144-2611 Sentence denotes Studies of SARS-CoV-1 indicate that T cell response against the S protein correlates with nAb titers and dominated the T cell response after natural infection, which also induced T cells active against the membrane (M) and N proteins, that memory T cell responses can persist even 11 years after infection, and that memory CD8+ T cells can protect mice from lethal challenge in the absence of memory CD4+ T cells and memory B cells (Li et al., 2008, Ng et al., 2016).
T633 2612-2809 Sentence denotes RBD-specific antiviral T cell responses have also been detected in people who have recovered from COVID-19, further validating its promise as a vaccine target (Braun et al., 2020, Ni et al., 2020).
T634 2811-2826 Sentence denotes Epitope Mapping
T635 2827-3079 Sentence denotes Although the antibodies targeting the RBD of the S protein have greater potential for providing cross-protective immunity, other fragments of the S protein and additional viral proteins have been investigated as target epitopes, especially for T cells.
T636 3080-3608 Sentence denotes Researchers have taken advantage of the genetic similarity between SARS-CoV-2 and SARS-CoV-1 and MERS-CoV and bioinformatics approaches to rapidly identify potential B and T cell epitopes in the S and other proteins, with many studies providing data regarding antigen presentation and antibody-binding properties and one study looking into the predicted evolution of epitopes (Ahmed et al., 2020, Baruah and Bose, 2020, Bhattacharya et al., 2020, Fast et al., 2020, Grifoni et al., 2020, Lon et al., 2020, Zheng and Song, 2020).
T637 3609-3840 Sentence denotes While the S protein has been found to be the most immunodominant protein in SARS-CoV-2, the M and N proteins also contain B and T cell epitopes, including some with high conservation with SARS-CoV-1 epitopes (Grifoni et al., 2020).
T638 3842-3858 Sentence denotes Vaccine Pipeline
T639 3859-4132 Sentence denotes For SARS-CoV-1 and MERS-CoV, animal studies and phase I clinical trials of potential vaccines targeting the S protein had encouraging results, with evidence of nAb induction and induction of cellular immunity (Lin et al., 2007, Martin et al., 2008, Modjarrad et al., 2019).
T640 4133-4249 Sentence denotes These findings are being translated into SARS-CoV-2 vaccine development efforts, hastening the progress drastically.
T641 4250-4409 Sentence denotes The WHO provided a report in April that reported 63 vaccine candidates in preclinical testing and three in clinical testing (World Health Organization, 2020b).
T642 4410-4516 Sentence denotes A recent search on May 1, 2020 on ClinicalTrials.gov revealed 10 registered vaccine candidates (Table 5 ).
T643 4517-4700 Sentence denotes The University of Pittsburgh is also looking to move their microneedle array vaccine candidate containing a codon-optimized S1 subunit protein into clinical trials (Kim et al., 2020).
T644 4701-4965 Sentence denotes Sanofi and GlaxoSmithKline (GSK) have recently reported their intent to collaborate and bring together Sanofi’s baculovirus expression system, which is used to produce the influenza virus vaccine, Flublok, to create an S protein vaccine adjuvanted with GSK’s AS03.
T645 4966-5166 Sentence denotes Sinovac Biotech will also enter testing in a clinical trial in China after it was found to protect rhesus macaques from viral challenge without signs of detectable immunopathology (Gao et al., 2020c).
T646 5167-5437 Sentence denotes Although some of these vaccine candidates are based on platforms that have been used or tested for other purposes, there remain questions regarding their safety and immunogenicity, including the longevity of any induced responses, that will require continual evaluation.
T647 5438-5505 Sentence denotes Table 5 Vaccine Candidates Currently Registered for Clinical Trials
T648 5506-5579 Sentence denotes Candidate Design Developer Similar Strategy ClinicalTrials.gov Identifier
T649 5580-5709 Sentence denotes mRNA-1273 LNP-encapsulated mRNA for full-length S protein ModernaTX CMV (John et al., 2018), ZKV (Pardi et al., 2017) NCT04283461
T650 5710-5891 Sentence denotes BNT162a1, b1, b2, c2 LNP-encapsulated mRNA vaccines with different formats of RNA and targets, two for larger S sequence and two for optimized RBD BioNTech SE and Pfizer NCT04368728
T651 5892-6035 Sentence denotes INO-4800 DNA vaccine for full-length S protein Inovio Pharmaceuticals MERS-CoV (Modjarrad et al., 2019), HPV (Trimble et al., 2015) NCT04336410
T652 6036-6196 Sentence denotes Ad5-nCoV adenovirus type 5 encoding full-length S protein CanSino Biologics EBV (Zhu et al., 2015, Zhu et al., 2017) NCT04313127 (phase I)NCT04341389 (phase II)
T653 6197-6348 Sentence denotes ChAdOx1 nCoV-19 adenovirus encoding full-length S protein University of Oxford MERS-CoV (Alharbi et al., 2017), IAV (Antrobus et al., 2014) NCT04324606
T654 6349-6547 Sentence denotes COVID-19 LV-SMENP-DC dendritic cells infected with lentivirus expressing SMENP minigenes to express COVID-19 antigens, together with activated CTLs Shenzhen Geno-Immune Medical Institute NCT04276896
T655 6548-6694 Sentence denotes COVID-19 aAPCs aAPCs infected with lentivirus expressing minigenes to express COVID-19 antigens Shenzhen Geno-Immune Medical Institute NCT04299724
T656 6695-6842 Sentence denotes bacTRL-Spike-1 live bacteria delivering plasmid encoding S protein Symvivo Corporation therapeutics reviewed (Charbonneau et al., 2020) NCT04334980
T657 6843-6950 Sentence denotes PiCoVacc inactivated SARS-CoV-2 vaccine Sinovac Biotech HAV, IAV, IBV, poliovirus, rabies virus NCT04352608
T658 6951-7053 Sentence denotes SARS-CoV-2 rS spike protein nanoparticle vaccine with or without Matrix-M adjuvant Novavax NCT04368988
T659 7054-7278 Sentence denotes aAPCs, artificial antigen-presenting cells; CMV, cytomegalovirus; EBV, Ebola virus; HAV, hepatitis A virus; HPV, human papillomavirus; IAV, influenza A virus; IBV, influenza B virus; LPN, lipid nanoparticle; ZKV, Zika virus.
T660 7280-7290 Sentence denotes Challenges
T661 7291-7496 Sentence denotes Although the development of a vaccine to protect against SARS-CoV-2 infection has progressed at an unprecedented rate and produced an impressive volume of candidates for testing, many challenges lie ahead.
T662 7497-7802 Sentence denotes The prior knowledge gained after SARS-CoV-1 was first discovered in 2003, and the subsequent emergence of MERS-CoV in 2012 provided a significant jumpstart, but the progress of SARS-CoV-2 vaccine development has already far outstripped the point of the blueprint created before COVID-19 became a pandemic.
T663 7803-8000 Sentence denotes While a variety of platforms are simultaneously being innovated or adapted, they each have strengths and limitations, many of which relate to the delicate balance between safety and immunogenicity.
T664 8001-8161 Sentence denotes Many shortcuts have been taken and will continue to be taken due to the urgency of the ongoing COVID-19 pandemic, but significant concerns need to be addressed.
T665 8162-8303 Sentence denotes One such concern involves the accumulating data supporting the initial assessment that COVID-19 is disproportionately severe in older adults.
T666 8304-8516 Sentence denotes In conjunction with the large body of work related to immune senescence, these findings indicate that vaccine design should take into consideration the impact of aging on vaccine efficacy (Nikolich-Žugich, 2018).
T667 8517-8794 Sentence denotes Furthermore, questions remain regarding the possibility of antibody-dependent enhancement of COVID-19, with in vitro experiments, animal studies, and two studies of COVID-19 patients supporting this possibility (Cao, 2020, Tetro, 2020, Zhang et al., 2020a, Zhao et al., 2020a).
T668 8795-8969 Sentence denotes Assuming vaccine candidates that can safely induce protective immune responses are identified, additional major hurdles will be the production and dissemination of a vaccine.
T669 8970-9268 Sentence denotes For some types of vaccines, large-scale production will not be as much of an issue, and infrastructure already in place to produce current Good Manufacturing Practice (cGMP)-quality biologics can be repurposed, but this will only be applicable to a subset of the candidates (Thanh Le et al., 2020).
T670 9269-9691 Sentence denotes In order to address the urgent need and stem the COVID-19 pandemic, regulatory agencies need to continue to support rapid testing and progression of vaccine candidates, companies need to disseminate important findings directly and openly, and researchers need to investigate correlates of protection using in-depth immune monitoring of patients with a broad range of clinical presentations and clinical trial participants.
T671 9692-9881 Sentence denotes The newly announced Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) is designed to bring together numerous governmental and industry entities to help address this need.