Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

ABSTRACT: Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)^1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID₅₀) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.

SUBMITTER: Saunders KO

PROVIDER: S-EPMC8528238 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Modeling pathogenesis of emergent and pre-emergent human coronaviruses in mice.

Project description:The emergence of highly pathogenic human coronaviruses (hCoVs) in the last two decades has illuminated their potential to cause high morbidity and mortality in human populations and disrupt global economies. Global pandemic concerns stem from their high mortality rates, capacity for human-to-human spread by respiratory transmission, and complete lack of approved therapeutic countermeasures. Limiting disease may require the development of virus-directed and host-directed therapeutic strategies due to the acute etiology of hCoV infections. Therefore, understanding how hCoV-host interactions cause pathogenic outcomes relies upon mammalian models that closely recapitulate the pathogenesis of hCoVs in humans. Pragmatism has largely been the driving force underpinning mice as highly effective mammalian models for elucidating hCoV-host interactions that govern pathogenesis. Notably, tractable mouse genetics combined with hCoV reverse genetic systems has afforded the concomitant manipulation of virus and host genetics to evaluate virus-host interaction networks in disease. In addition to assessing etiologies of known hCoVs, mouse models have clinically predictive value as tools to appraise potential disease phenotypes associated with pre-emergent CoVs. Knowledge of CoV pathogenic potential before it crosses the species barrier into the human population provides a highly desirable preclinical platform for addressing global pathogen preparedness, an overarching directive of the World Health Organization. Although we recognize that results obtained in robust mouse models require evaluation in non-human primates, we focus this review on the current state of hCoV mouse models, their use as tractable complex genetic organisms for untangling complex hCoV-host interactions, and as pathogenesis models for preclinical evaluation of novel therapeutic interventions.

| S-EPMC6132729 | biostudies-literature

A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice.

Project description:SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.

| S-EPMC8095197 | biostudies-literature

Prepare for the Future: Dissecting the Spike to Seek Broadly Neutralizing Antibodies and Universal Vaccine for Pandemic Coronaviruses.

Project description:Learning from the lengthy fight against HIV-1, influenza, and Ebola virus infection, broadly neutralizing antibodies (bnAbs), directed at conserved regions of surface proteins crucial to virus entry (Env, hemagglutinin, and GP, respectively), are an essential resource for passive as well as active immunization. Rare in their emergence and antigen recognition mode, bnAbs are active toward a large set of different viral strains. Isolation, characterization and production of bnAbs lead to their possible use in passive immunotherapy and form the basis for an educated effort in the development of vaccines for universal coverage. SARS-CoV-2-specific antibodies targeting the spike receptor binding domain (RBD) may lead to antibody dependent enhancement (ADE) of infection, possibly hampering the field of vaccine development. This perspective points to the identification of conserved regions in the spike of SARS-CoV-2, SARS-CoV, and MERS-CoV through investigation, dissection and recombinant production of isolated moieties. These spike moieties should be capable of independent folding and allow the detection as well as the elicitation of bnAbs, thus setting the basis for an effective passive immunotherapy and the development of a universal vaccine against human epidemic coronaviruses (HCoVs). SARS, MERS and, most of all, COVID-19 demonstrate that humanity is the target of HCoV, preparedness for future hits is thus no longer an option.

| S-EPMC7490329 | biostudies-literature

Enhanced neutralizing antibody titers and Th1 polarization from a novel Escherichia coli derived pandemic influenza vaccine.

Project description:Influenza pandemics can spread quickly and cost millions of lives; the 2009 H1N1 pandemic highlighted the shortfall in the current vaccine strategy and the need for an improved global response in terms of shortening the time required to manufacture the vaccine and increasing production capacity. Here we describe the pre-clinical assessment of a novel 2009 H1N1 pandemic influenza vaccine based on the E. coli-produced HA globular head domain covalently linked to virus-like particles derived from the bacteriophage Q?. When formulated with alum adjuvant and used to immunize mice, dose finding studies found that a 10 µg dose of this vaccine (3.7 µg globular HA content) induced antibody titers comparable to a 1.5 µg dose (0.7 µg globular HA content) of the licensed 2009 H1N1 pandemic vaccine Panvax, and significantly reduced viral titers in the lung following challenge with 2009 H1N1 pandemic influenza A/California/07/2009 virus. While Panvax failed to induce marked T cell responses, the novel vaccine stimulated substantial antigen-specific interferon-? production in splenocytes from immunized mice, alongside enhanced IgG2a antibody production. In ferrets the vaccine elicited neutralizing antibodies, and following challenge with influenza A/California/07/2009 virus reduced morbidity and lowered viral titers in nasal lavages.

| S-EPMC3799843 | biostudies-literature

Heritability of vaccine-induced measles neutralizing antibody titers.

Project description:Understanding how genetics influences inter-individual variation of antibody titers in response to measles vaccination is vital to understanding possible sources of vaccine failure as well as improved vaccine development. Although it is recognized that both the human leukocyte antigen (HLA) genes and the immunoglobulin allotype genes play significant roles in immune response, there is significant variation in antibody titers that is not explained by these genes. To obtain a more complete estimate of the role of the entire genome, we used a large panel of single nucleotide polymorphisms to estimate the heritability of antibody response to measles vaccine. Based on 935 subjects with European ancestry, we estimated the heritability to be 49% (standard error 0.17). We also estimated the heritability attributable to each chromosome, and found a large range in chromosome-specific heritabilities. Notably, chromosome 1 had the largest estimate (28%), while chromosome 6, which harbors HLA, had an estimated heritability of 13%. Compared with a prior study of twins in the same community, which resulted in a heritability estimate of 88.5%, our study suggests there are either many rare genetic variants, or many common genetic variants of small effect sizes that contribute to variations of antibody titers in response to measles vaccine.

| S-EPMC5548390 | biostudies-literature

High activity of an affinity-matured ACE2 decoy against Omicron SARS-CoV-2 and pre-emergent coronaviruses.

Project description:The viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly its cell-binding spike protein gene, has undergone rapid evolution during the coronavirus disease 2019 (COVID-19) pandemic. Variants including Omicron BA.1 and Omicron BA.2 now seriously threaten the efficacy of therapeutic monoclonal antibodies and vaccines that target the spike protein. Viral evolution over a much longer timescale has generated a wide range of genetically distinct sarbecoviruses in animal populations, including the pandemic viruses SARS-CoV-2 and SARS-CoV-1. The genetic diversity and widespread zoonotic potential of this group complicates current attempts to develop drugs in preparation for the next sarbecovirus pandemic. Receptor-based decoy inhibitors can target a wide range of viral strains with a common receptor and may have intrinsic resistance to escape mutant generation and antigenic drift. We previously generated an affinity-matured decoy inhibitor based on the receptor target of the SARS-CoV-2 spike protein, angiotensin-converting enzyme 2 (ACE2), and deployed it in a recombinant adeno-associated virus vector (rAAV) for intranasal delivery and passive prophylaxis against COVID-19. Here, we demonstrate the exceptional binding and neutralizing potency of this ACE2 decoy against SARS-CoV-2 variants including Omicron BA.1 and Omicron BA.2. Tight decoy binding tracks with human ACE2 binding of viral spike receptor-binding domains across diverse clades of coronaviruses. Furthermore, in a coronavirus that cannot bind human ACE2, a variant that acquired human ACE2 binding was bound by the decoy with nanomolar affinity. Considering these results, we discuss a strategy of decoy-based treatment and passive protection to mitigate the ongoing COVID-19 pandemic and future airway virus threats.

| S-EPMC9409550 | biostudies-literature

Coronavirus Pseudotypes for All Circulating Human Coronaviruses for Quantification of Cross-Neutralizing Antibody Responses.

Project description:The novel coronavirus SARS-CoV-2 is the seventh identified human coronavirus. Understanding the extent of pre-existing immunity induced by seropositivity to endemic seasonal coronaviruses and the impact of cross-reactivity on COVID-19 disease progression remains a key research question in immunity to SARS-CoV-2 and the immunopathology of COVID-2019 disease. This paper describes a panel of lentiviral pseudotypes bearing the spike (S) proteins for each of the seven human coronaviruses (HCoVs), generated under similar conditions optimized for high titre production allowing a high-throughput investigation of antibody neutralization breadth. Optimal production conditions and most readily available permissive target cell lines were determined for spike-mediated entry by each HCoV pseudotype: SARS-CoV-1, SARS-CoV-2 and HCoV-NL63 best transduced HEK293T/17 cells transfected with ACE2 and TMPRSS2, HCoV-229E and MERS-CoV preferentially entered HUH7 cells, and CHO cells were most permissive for the seasonal betacoronavirus HCoV-HKU1. Entry of ACE2 using pseudotypes was enhanced by ACE2 and TMPRSS2 expression in target cells, whilst TMPRSS2 transfection rendered HEK293T/17 cells permissive for HCoV-HKU1 and HCoV-OC43 entry. Additionally, pseudotype viruses were produced bearing additional coronavirus surface proteins, including the SARS-CoV-2 Envelope (E) and Membrane (M) proteins and HCoV-OC43/HCoV-HKU1 Haemagglutinin-Esterase (HE) proteins. This panel of lentiviral pseudotypes provides a safe, rapidly quantifiable and high-throughput tool for serological comparison of pan-coronavirus neutralizing responses; this can be used to elucidate antibody dynamics against individual coronaviruses and the effects of antibody cross-reactivity on clinical outcome following natural infection or vaccination.

| S-EPMC8402765 | biostudies-literature

Lineage-specific epitope profiles for HPAI H5 pre-pandemic vaccine selection and evaluation.

Project description:Multiple highly pathogenic avian influenza (HPAI) H5 viruses continue to co-circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation.In this study, we aimed to predict and map the diversity of CD8+ T-cell epitopes among H5 hemagglutinin (HA) gene lineages to estimate CD8+ T-cell immunity in humans induced by vaccine candidates.A dataset consisting of 1125 H5 HA sequences collected between 1996 and 2017 from avian and humans was assembled for phylogenetic and lineage-specific epitope analyses. Conserved epitopes were predicted from WHO-endorsed vaccine candidates and representative clade-defining strains by pairwise comparison with Immune Epitope Database (IEDB). The distribution of predicted epitopes was mapped to each HPAI H5 lineage. We assume that high similarity and conservancy of predicted epitopes from vaccine candidates among all circulating HPAI H5 lineages is correlated with high immunity.A total of 49 conserved CD8+ T-cell epitopes were predicted at 28 different amino acid positions of the HA protein. Mapping these epitopes to the phylogenetic tree allowed us to develop epitope profiles, or "fingerprints," for each HPAI H5 lineage. Vaccine epitope percentage analyses showed some epitope profiles were highly conserved for all H5 isolates and may be valuable for universal vaccine design. However, the positions with low coverage may explain why the vaccine candidates do not always function well.These findings demonstrate that our analytical approach to evaluate conserved CD8+ T-cell epitope prediction in a phylogenetic framework may provide important insights for computational design of vaccine selection and future epitope-based design.

| S-EPMC5963872 | biostudies-other

Coronaviruses pandemics: Can neutralizing antibodies help?

Project description:For the first time in Homo sapiens history, possibly, most of human activities is stopped by coronavirus disease 2019 (COVID-19). Nearly eight billion people of this world are facing a great challenge, maybe not "to be or not to be" yet, but unpredictable. What happens to other major pandemics in the past, and how human beings went through these hurdles? The human body is equipped with the immune system that can recognize, respond and fight against pathogens such as viruses. Following the innate response, immune system processes the adaptive response by which each pathogen is encoded and recorded in memory system. The humoral reaction containing cytokines and antibodies is expected to activate when the pathogens come back. Exploiting this nature of body protection, neutralizing antibodies have been investigated. Learning from past, in parallel to SARS-CoV-2, other coronaviruses SARS-CoV and MERS-CoV who caused previous pandemics, are recalled in this review. We here propose insights of origin and characteristics and perspective for the future of antibodies development.

| S-EPMC7243778 | biostudies-literature

CD4+ T-cell expansion predicts neutralizing antibody responses to monovalent, inactivated 2009 pandemic influenza A(H1N1) virus subtype H1N1 vaccine.

Project description:BackgroundThe ability of influenza vaccines to elicit CD4(+) T cells and the relationship between induction of CD4(+) T cells and vaccine-induced neutralizing antibody responses has been controversial. The emergence of swine-origin 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique opportunity to examine responses to an influenza vaccine composed of both novel and previously encountered antigens and to probe the relationship between B-cell and T-cell responses to vaccination.MethodsWe tracked CD4(+) T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4(+) T-cell response was evaluated using cytokine enzyme-linked immunosorbent spot assays in conjugation with peptide pools representing distinct influenza virus proteins.ResultsOur studies revealed that vaccination induced readily detectable CD4(+) T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins. Interestingly, expansion of HA-specific CD4(+) T cells was most tightly correlated with the antibody response.ConclusionsThese results indicate that CD4(+) T-cell expansion may be a limiting factor in development of neutralizing antibody responses to pandemic influenza vaccines and suggest that approaches to facilitate CD4(+) T-cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.

| S-EPMC3532833 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data