Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice.

ABSTRACT: The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10¹³ or 10¹⁴ viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.

SUBMITTER: Turan RD

PROVIDER: S-EPMC8339061 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Intranasal administration of cold-adapted live-attenuated SARS-CoV-2 candidate vaccine confers protection against SARS-CoV-2

Project description:With the COVID-19 pandemic globally, the ongoing threat of new challenges of mucosal infections was once again reminded human beings. Hence, access to the next-generation vaccine to elicit mucosal immunity is required to reduce virus shedding. SARS-CoV-2 retains a unique polybasic cleavage motif in its spike protein, recognized by the host furin protease. The proteolytic furin cleavage site at the junction of S1/S2 glycoprotein plays a key role in the pathogenesis of SARS-CoV-2. Here, we examined the protective immunity of a double-deleted PRRA/GTNGTKR motifs cold-adapted live-attenuated candidate vaccines as a called “KaraVac.” using a hamster animal model of infected attenuated SARS-CoV-2. The KaraVac vaccinated hamsters were challenged against the wild-type (WT) SARS-CoV-2. No apparent bodyweight loss and histopathological lesions were observed in the hamsters. The establishment of sterilizing immunity was induced via stimulating a robust neutralizing antibody (NAb) response in a hamster model. Consequently, deletions in the spike sequence and inoculation into hamsters provide resistance to the subsequent challenge with WT SARS-CoV-2. We have suggested that deletion of the furin cleavage site and GTNGTKR motifs in the spike sequence attenuates the virus from the parental strain and can be used as a potent immunogen. Graphical Abstract Graphical Abstract Image, graphical abstract.

| S-EPMC9270963 | biostudies-literature

An adenovirus-vectored COVID-19 vaccine confers protection from SARS-COV-2 challenge in rhesus macaques.

Project description:The rapid spread of coronavirus SARS-CoV-2 greatly threatens global public health but no prophylactic vaccine is available. Here, we report the generation of a replication-incompetent recombinant serotype 5 adenovirus, Ad5-S-nb2, carrying a codon-optimized gene encoding Spike protein (S). In mice and rhesus macaques, intramuscular injection with Ad5-S-nb2 elicits systemic S-specific antibody and cell-mediated immune (CMI) responses. Intranasal inoculation elicits both systemic and pulmonary antibody responses but weaker CMI response. At 30 days after a single vaccination with Ad5-S-nb2 either intramuscularly or intranasally, macaques are protected against SARS-CoV-2 challenge. A subsequent challenge reveals that macaques vaccinated with a 10-fold lower vaccine dosage (1?×?1010 viral particles) are also protected, demonstrating the effectiveness of Ad5-S-nb2 and the possibility of offering more vaccine dosages within a shorter timeframe. Thus, Ad5-S-nb2 is a promising candidate vaccine and warrants further clinical evaluation.

| S-EPMC7442803 | biostudies-literature

A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques.

Project description:BackgroundPersistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, conceived in 2020, that evoke protective spike antibody responses are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.MethodsUsing a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 × 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms and viral load, chest radiographs, and sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis.ResultsVaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques.ConclusionsWe demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in nonhuman primates.

| S-EPMC8158516 | biostudies-literature

DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model.

Project description:SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

| S-EPMC8789660 | biostudies-literature

A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates.

Project description:Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>10 4 ) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log 10 reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.

| S-EPMC8288147 | biostudies-literature

X-ray Irradiated Vaccine Confers protection against Pneumonia caused by Pseudomonas aeruginosa.

Project description:Pseudomonas aeruginosa is a gram-negative bacterium and one of the leading causes of nosocomial infection worldwide, however, no effective vaccine is currently available in the market. Here, we demonstrate that inactivation of the bacteria by X-ray irradiation inhibits its replication capability but retained antigenic expression functionally thus allowing its use as a potential vaccine. Mice immunized by this vaccine were challenged by the parental strain, the O-antigen-homologous strain PAO-1 (O2/O5) and heterologous strain PAO-6 (O6) in an acute pneumonia model. We further measured the protective effect of the vaccine, as well as host innate and cellular immunity responses. We found immunized mice could protect against both strains. Notably, the antiserum only had significant protective role against similar bacteria, while adoptive transfer of lymphocytes significantly controlled the spread of the virulent heterologous serogroup PAO-6 infection, and the protective role could be reversed by CD4 rather than CD8 antibody. We further revealed that vaccinated mice could rapidly recruit neutrophils to the airways early after intranasal challenge by PAO-6, and the irradiated vaccine was proved to be protective by the generated CD4(+) IL-17(+) Th17 cells. In conclusion, the generation of inactivated but metabolically active microbes is a promising strategy for safely vaccinating against Pseudomonas aeruginosa.

| S-EPMC4754647 | biostudies-literature

A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge.

Project description:The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials.

| S-EPMC7427994 | biostudies-literature

A single dose of recombinant VSV-?G-spike vaccine provides protection against SARS-CoV-2 challenge.

Project description:The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we show the development of a replication competent recombinant VSV-?G-spike vaccine, in which the glycoprotein of VSV is replaced by the spike protein of SARS-CoV-2. In-vitro characterization of this vaccine indicates the expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. A golden Syrian hamster in-vivo model for COVID-19 is implemented. We show that a single-dose vaccination results in a rapid and potent induction of SARS-CoV-2 neutralizing antibodies. Importantly, vaccination protects hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss, and alleviation of the extensive tissue damage and viral loads in lungs and nasal turbinates. Taken together, we suggest the recombinant VSV-?G-spike as a safe, efficacious and protective vaccine against SARS-CoV-2.

| S-EPMC7745033 | biostudies-literature

Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2.

Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 μg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.

| S-EPMC7275151 | biostudies-literature

A two-adjuvant multiantigen candidate vaccine induces superior protective immune responses against SARS-CoV-2 challenge.

Project description:An ideal vaccine against SARS-CoV-2 is expected to elicit broad immunity to prevent viral infection and disease, with efficient viral clearance in the upper respiratory tract (URT). Here, the N protein and prefusion-full S protein (SFLmut) are combined with flagellin (KF) and cyclic GMP-AMP (cGAMP) to generate a candidate vaccine, and this vaccine elicits stronger systemic and mucosal humoral immunity than vaccines containing other forms of the S protein. Furthermore, the candidate vaccine administered via intranasal route can enhance local immune responses in the respiratory tract. Importantly, human ACE2 transgenic mice given the candidate vaccine are protected against lethal SARS-CoV-2 challenge, with superior protection in the URT compared with that in mice immunized with an inactivated vaccine. In summary, the developed vaccine can elicit a multifaceted immune response and induce robust viral clearance in the URT, which makes it a potential vaccine for preventing disease and infection of SARS-CoV-2.

| S-EPMC8610932 | 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