Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages.

ABSTRACT: A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from lethal challenges by IBV of both genetic lineages, demonstrating its breadth of protection. The protection was not mediated by neutralizing antibodies but robust antibody-dependent cellular cytotoxicity and cell-mediated immune responses. Complete protection of the animals required the entire codon-optimized HA2 sequence that elicited a balanced immune response, whereas truncated vaccines without either the fusion peptide or the transmembrane domain reduced the efficacy of protection. Finally, the vaccines did not demonstrate any sign of disease exacerbation following lung pathology and morbidity monitoring. Collectively, these data suggest that it could be worth further exploring this prototype universal vaccine because of its considerable efficacy, safety, and breadth of protection.

SUBMITTER: Gravel C

PROVIDER: S-EPMC8586812 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Nonreplicating influenza A virus vaccines confer broad protection against lethal challenge.

Project description:UNLABELLED:New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppression of the hemagglutinin signal sequence, with the corresponding H1N1 and H5N1 cold-adapted (ca) live attenuated influenza virus vaccines in mice and ferrets. Administration of two doses of H1 or H5 S-FLU vaccines protected mice and ferrets from lethal challenge with homologous, heterologous, and heterosubtypic influenza viruses, and two doses of S-FLU and ca vaccines yielded comparable effects. Importantly, when ferrets immunized with one dose of H1 S-FLU or ca vaccine were challenged with the homologous H1N1 virus, the challenge virus failed to transmit to naive ferrets by the airborne route. S-FLU technology can be rapidly applied to any emerging influenza virus, and the promising preclinical data support further evaluation in humans. IMPORTANCE:Influenza viruses continue to represent a global public health threat, and cross-protective vaccines are needed to prevent seasonal and pandemic influenza. Currently licensed influenza vaccines are based on immunity to the hemagglutinin protein that is highly variable. However, T cell responses directed against highly conserved viral proteins contribute to clearance of the virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses. In this study, two nonreplicating pseudotyped influenza virus vaccines were compared with their corresponding live attenuated influenza virus vaccines, and both elicited robust protection against homologous and heterosubtypic challenge in mice and ferrets, making them promising candidates for further evaluation in humans.

| S-EPMC4620468 | biostudies-literature

Protein nanoparticle vaccine based on flagellin carrier fused to influenza conserved epitopes confers full protection against influenza A virus challenge.

Project description:Currently marketed influenza vaccines only confer protection against matching influenza virus strains. The influenza A composition of these vaccines needs to be annually updated. Vaccines that target conserved epitopes of influenza viruses would in principle offer broad cross-protection against influenza A viruses. In our study, we investigated the specific immune responses and protective efficacy of protein nanoparticles based on fusion proteins of flagellin carrier linked to conserved influenza epitopes. We designed fusion proteins by replacing the hyperimmunogenic region of flagellin (FliC) with four tandem copies of the ectodomain of matrix protein 2 (f4M2e), H1 HA2 domain (fHApr8) or H3 HA2 domain (fHAaichi). Protein nanoparticles fabricated from these fusion proteins by using DTSSP crosslinking retained Toll-like receptor 5 agonist activity of FliC. Intranasal immunization with f4M2e, f4M2e/fHApr8 or f4M2e/fHAaichi nanoparticles induced vaccine antigen-specific humoral immune responses. It was also found that the incorporation of the H1 HA2 domain into f4M2e/fHApr8 nanoparticles boosted M2e specific antibody responses. Immunized mice were fully protected against lethal doses of virus challenge.

| S-EPMC5526067 | biostudies-literature

Purified Inactivated Zika Vaccine Candidates Afford Protection against Lethal Challenge in Mice.

Project description:In response to the 2016 global public health emergency of international concern announced by the World Health Organization surrounding Zika virus (ZIKV) outbreaks, we developed a purified inactivated Zika virus vaccine (PIZV) candidate from ZIKV strain PRVABC59, isolated during the outbreak in 2015. The virus isolate was plaque purified, creating six sub-isolated virus stocks, two of which were selected to generate PIZV candidates for preclinical immunogenicity and efficacy evaluation in mice. The alum-adjuvanted PIZV candidates were highly immunogenic in both CD-1 and AG129 mice after a 2-dose immunization. Further, AG129 mice receiving 2 doses of PIZV formulated with alum were fully protected against lethal ZIKV challenge and mouse immune sera elicited by the PIZV candidates were capable of neutralizing ZIKVs of both African and Asian genetic lineages in vitro. Additionally, passive immunization of naïve mice with ZIKV-immune serum showed strong positive correlation between neutralizing ZIKV antibody (NAb) titers and protection against lethal challenge. This study supported advancement of the PIZV candidate toward clinical development.

| S-EPMC6220238 | biostudies-literature

A single-cycle replicable Rift Valley fever phlebovirus vaccine carrying a mutated NSs confers full protection from lethal challenge in mice.

Project description:Rift Valley fever phlebovirus (RVFV) is a pathogen of Rift Valley fever, which is a mosquito-borne zoonotic disease for domestic livestock and humans in African countries. Currently, no approved vaccine is available for use in non-endemic areas. The MP-12 strain is so far the best live attenuated RVFV vaccine candidate because of its good protective efficacy in animal models. However, there are safety concerns for use of MP-12 in humans. We previously developed a single-cycle replicable MP-12 (scMP-12) which lacks NSs gene and undergoes only a single round of viral replication because of its impaired ability to induce membrane-membrane fusion. In the present study, we generated an scMP-12 mutant (scMP-12-mutNSs) carrying a mutant NSs, which degrades double-stranded RNA-dependent protein kinase R but does not inhibit host transcription. Immunization of mice with a single dose (105 PFU) of scMP-12-mutNSs elicited RVFV neutralizing antibodies and high titers of anti-N IgG production and fully protected the mice from lethal wild-type RVFV challenge. Immunogenicity and protective efficacy of scMP-12-mutNSs were better than scMP-12, demonstrating that scMP-12-mutNSs is a more efficacious vaccine candidate than scMP-12. Furthermore, our data suggested that RVFV vaccine efficacy can be improved by using this specific NSs mutant.

| S-EPMC6244155 | biostudies-literature

Immunization by vaccine-coated microneedle arrays protects against lethal influenza virus challenge.

Project description:Influenza prophylaxis would benefit from a simple method to administer influenza vaccine into skin without the need for hypodermic needles. In this study, solid metal microneedle arrays (MNs) were investigated as a system for cutaneous vaccine delivery using influenza virus antigen. The MNs with 5 monument-shaped microneedles per array were produced and coated with inactivated influenza virus A/PR/8/34 (IIV). As much as 10 microg of viral proteins could be coated onto an array of 5 microneedles, and the coated IIV was delivered into skin at high efficiency within minutes. The coated MNs were used to immunize mice in comparison with conventional intramuscular injection at the same dose. Analysis of immune responses showed that a single immunization with IIV-coated MNs induced strong antibody responses against influenza virus, with significant levels of hemagglutination inhibition activities (>1:40), which were comparable to those induced by conventional intramuscular immunization. Moreover, mice immunized by a single dose of IIV coated on MNs were effectively protected against lethal challenge by a high dose of mouse-adapted influenza virus A/PR/8/34. These results show that MNs are highly effective as a simple method of vaccine delivery to elicit protective immune responses against virus infection.

| S-EPMC2683119 | biostudies-literature

Immunization with a live attenuated H7N9 influenza vaccine protects mice against lethal challenge.

Project description:The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this study, a cold-adapted (ca), live attenuated monovalent reassortant influenza H7N9 virus (Ah01/AA ca) was generated using reverse genetics that contained hemagglutinin (HA) and neuraminidase (NA) genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus (Ah01/H7N9); the remaining six backbone genes derived from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus). Ah01/AA ca virus exhibited temperature sensitivity (ts), ca, and attenuation (att) phenotypes. Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9 (A/Anhui/01/2013). Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates.

| S-EPMC4401572 | biostudies-literature

Prevention of influenza virus shedding and protection from lethal H1N1 challenge using a consensus 2009 H1N1 HA and NA adenovirus vector vaccine.

Project description:Vaccines against emerging pathogens such as the 2009 H1N1 pandemic virus can benefit from current technologies such as rapid genomic sequencing to construct the most biologically relevant vaccine. A novel platform (Ad5 [E1-, E2b-]) has been utilized to induce immune responses to various antigenic targets. We employed this vector platform to express hemagglutinin (HA) and neuraminidase (NA) genes from 2009 H1N1 pandemic viruses. Inserts were consensuses sequences designed from viral isolate sequences and the vaccine was rapidly constructed and produced. Vaccination induced H1N1 immune responses in mice, which afforded protection from lethal virus challenge. In ferrets, vaccination protected from disease development and significantly reduced viral titers in nasal washes. H1N1 cell mediated immunity as well as antibody induction correlated with the prevention of disease symptoms and reduction of virus replication. The Ad5 [E1-, E2b-] should be evaluated for the rapid development of effective vaccines against infectious diseases.

| S-EPMC3578229 | biostudies-literature

A Synthetic Micro-Consensus DNA Vaccine Generates Comprehensive Influenza A H3N2 Immunity and Protects Mice Against Lethal Challenge by Multiple H3N2 Viruses.

Project description:Influenza A H3N2 viruses circulate globally, leading to substantial morbidity and mortality. Commercially available, antigen-matched influenza vaccines must be updated frequently to match dynamic sequence variability in immune epitopes, especially within viral influenza A H3N2 hemagglutinin (H3). In an effort to create comprehensive immune responses against H3N2, four micro-consensus antigens were designed to mimic the sequence and antigenic diversity of H3. Synthetic plasmid DNA constructs were developed to express each micro-consensus immunogen and combined into a multi-antigen DNA vaccine cocktail, pH3HA. Facilitated delivery of pH3HA via intramuscular electroporation in mice induced comprehensive, potent humoral responses against diverse seasonal H3N2 viruses that circulated between 1968 and the present. Vaccination with pH3HA also induced an antigen-specific cellular cytokine response. Mice immunized with pH3HA were protected against lethal challenge using two distinct H3N2 viruses, highlighting the heterologous protection afforded by synthetic micro-consensus immunogens. These findings warrant further study of the DNA vaccine micro-consensus platform for broad protection against influenza viruses.

| S-EPMC6152850 | biostudies-literature

Both haemagglutinin-specific antibody and T cell responses induced by a chimpanzee adenoviral vaccine confer protection against influenza H7N9 viral challenge.

Project description:Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA vaccine prime-adenovirus boost regimen induced potent immune responses in animals and completely protected mice from lethal H7N9 influenza viral challenge. A post-immunization serum transfer experiment showed that antibody responses could completely protect against lethal challenge, while a T cell depletion experiment indicated that HA-specific CD8+ T cells responses also contributed to protection. Therefore, both HA-specific humoral immunity and cellular immunity play important roles in the protection. These data suggest that the chimpanzee adenovirus expressing HA is a promising vaccine candidate for H7N9 virus or other influenza viral subtypes.

| S-EPMC5431854 | biostudies-literature

Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge.

Project description:Crimean-Congo hemorrhagic fever (CCHF) is an acute, often fatal viral disease characterized by rapid onset of febrile symptoms followed by hemorrhagic manifestations. The etiologic agent, CCHF orthonairovirus (CCHFV), can infect several mammals in nature but only seems to cause clinical disease in humans. Over the past two decades there has been an increase in total number of CCHF case reports, including imported CCHF patients, and an expansion of CCHF endemic areas. Despite its increased public health burden there are currently no licensed vaccines or treatments to prevent CCHF. We here report the development and assessment of the protective efficacy of an adenovirus (Ad)-based vaccine expressing the nucleocapsid protein (N) of CCHFV (Ad-N) in a lethal immunocompromised mouse model of CCHF. The results show that Ad-N can protect mice from CCHF mortality and that this platform should be considered for future CCHFV vaccine strategies.

| S-EPMC6062107 | 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