Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Skin vaccination with dissolvable microneedle patches incorporating influenza neuraminidase and flagellin protein nanoparticles induces broad immune protection against multiple influenza viruses.

ABSTRACT: We generated self-adjuvanted protein nanoparticles of conserved influenza antigens and immunized mice via skin vaccination with dissolvable microneedle patches (MNPs) to increase the strength and breadth of immune responses. We produced M2e nanoparticles via ethanol desolvation, and double-layered NA1/M2e (shell/core), NA1-FliC/M2e, NA2/M2e, and NA2-FliC/M2e protein nanoparticles by chemically crosslinking influenza NA and flagellin (FliC) onto the surfaces of the M2e nanoparticles. The resulting nanoparticles retained FliC TLR5 innate signaling activity and significantly increased antigen-uptake and dendritic cell maturation in vitro. We incorporated the nanoparticles into MNPs for skin vaccination in mice. The nanoparticle MNPs significantly increased M2e and NA-specific antibody levels, the numbers of germinal center B cells, and IL-4 positive splenocytes. Double-layered nanoparticle MNP skin vaccination protected mice against homologous and heterosubtypic influenza viruses. Our results demonstrated that MNP skin vaccination of NA-FliC/M2e nanoparticles could be developed into a standalone or synergistic component of a universal influenza vaccine strategy.

SUBMITTER: Wang Y

PROVIDER: S-EPMC8232372 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Technology update: dissolvable microneedle patches for vaccine delivery.

Project description:Despite vaccination representing one of the greatest advances of modern preventative medicine, there remain significant challenges in vaccine distribution, delivery and compliance. Dissolvable microarray patches or dissolving microneedles (DMN) have been proposed as an innovative vaccine delivery platform that could potentially revolutionize vaccine delivery and circumvent many of the challenges faced with current vaccine strategies. DMN, due to their ease of use, lack of elicitation of pain response, self-disabling nature and ease of transport and distribution, offer an attractive delivery option for vaccines. Additionally, as DMN inherently targets the uppermost skin layers, they facilitate improved vaccine efficacy, due to direct targeting of skin antigen-presenting cells. A plethora of publications have demonstrated the efficacy of DMN vaccination for a range of vaccines, with influenza receiving particular attention. However, before the viable adoption of DMN for vaccination purposes in a clinical setting, a number of fundamental questions must be addressed. Accordingly, this review begins by introducing some of the key barriers faced by current vaccination approaches and how DMN can overcome these challenges. We introduce some of the recent advances in the field of DMN technology, highlighting the potential impact DMN could have, particularly in countries of the developing world. We conclude by reflecting on some of the key questions that remain unanswered and which warrant further investigation before DMNs can be utilized in clinical settings.

| S-EPMC6756839 | biostudies-other

Rapidly-dissolvable microneedle patches via a highly scalable and reproducible soft lithography approach.

Project description:Microneedle devices for transdermal drug delivery have recently become an attractive method to overcome the diffusion-limiting epidermis and effectively transport therapeutics to the body. Here, we demonstrate the fabrication of highly reproducible and completely dissolvable polymer microneedles on flexible water-soluble substrates. These biocompatible microneedles (made by using a soft lithography process known as PRINT) showed efficacy in piercing both murine and human skin samples and delivering a fluorescent drug surrogate to the tissue.

| S-EPMC4262250 | biostudies-literature

Dissolving polymer microneedle patches for influenza vaccination.

Project description:Influenza prophylaxis would benefit from a vaccination method enabling simplified logistics and improved immunogenicity without the dangers posed by hypodermic needles. Here we introduce dissolving microneedle patches for influenza vaccination using a simple patch-based system that targets delivery to skin's antigen-presenting cells. Microneedles were fabricated using a biocompatible polymer encapsulating inactivated influenza virus vaccine for insertion and dissolution in the skin within minutes. Microneedle vaccination generated robust antibody and cellular immune responses in mice that provided complete protection against lethal challenge. Compared to conventional intramuscular injection, microneedle vaccination resulted in more efficient lung virus clearance and enhanced cellular recall responses after challenge. These results suggest that dissolving microneedle patches can provide a new technology for simpler and safer vaccination with improved immunogenicity that could facilitate increased vaccination coverage.

| S-EPMC2917494 | biostudies-literature

Intranasal immunization with influenza VLPs incorporating membrane-anchored flagellin induces strong heterosubtypic protection.

Project description:We demonstrated previously that the incorporation of a membrane-anchored form of flagellin into influenza virus-like particles (VLPs) improved the immunogenicity of VLPs significantly, inducing partially protective heterosubtypic immunity by intramuscular immunization. Because the efficacy of mucosal vaccination is highly dependent on an adjuvant, and is particularly effective for preventing mucosal infections such as influenza, we determined whether the membrane-anchored flagellin is an efficient adjuvant for VLP vaccines by a mucosal immunization route. We compared the adjuvant effect of membrane-anchored and soluble flagellins for immunization with influenza A/PR8 (H1N1) VLPs by the intranasal route in a mouse model. The results demonstrate that membrane-anchored flagellin is an effective adjuvant for intranasal (IN) immunization, inducing enhanced systemic and mucosal antibody responses. High cellular responses were also observed as shown by cytokine production in splenocyte cultures when stimulated with viral antigens. All mice immunized with flagellin-containing VLPs survived challenge with a high lethal dose of homologous virus as well as a high dose heterosubtypic virus challenge (40 LD(50) of A/Philippines/82, H3N2). In contrast, no protection was observed with a standard HA/M1 VLP group upon heterosubtypic challenge. Soluble flagellin exhibited a moderate adjuvant effect when co-administered with VLPs by the mucosal route, as indicated by enhanced systemic and mucosal responses and partial heterosubtypic protection. The membrane-anchored form of flagellin incorporated together with antigen into influenza VLPs is effective as an adjuvant by the mucosal route and unlike standard VLPs, immunization with such chimeric VLPs elicits protective immunity to challenge with a distantly related influenza A virus.

| S-EPMC2993933 | biostudies-literature

Microneedle patches: usability and acceptability for self-vaccination against influenza.

Project description:While therapeutic drugs are routinely self-administered by patients, there is little precedent for self-vaccination. Convenient self-vaccination may expand vaccination coverage and reduce administration costs. Microneedle patches are in development for many vaccines, but no reports exist on usability or acceptability. We hypothesized that naïve patients could apply patches and that self-administered patches would improve stated intent to receive an influenza vaccine. We conducted a randomized, repeated measures study with 91 venue-recruited adults. To simulate vaccination, subjects received placebo microneedle patches given three times by self-administration and once by the investigator, as well as an intramuscular injection of saline. Seventy participants inserted patches with thumb pressure alone and the remainder used snap-based devices that closed shut at a certain force. Usability was assessed by skin staining and acceptability was measured with an adaptive-choice analysis. The best usability was seen with the snap device, with users inserting a median value of 93-96% of microneedles over three repetitions. When a self-administered microneedle patch was offered, intent to vaccinate increased from 44% to 65% (CI: 55-74%). The majority of those intending vaccination would prefer to self-vaccinate: 64% (CI: 51-75%). There were no serious adverse events associated with use of microneedle patches. The findings from this initial study indicate that microneedle patches for self-vaccination against influenza are usable and may lead to improved vaccination coverage.

| S-EPMC3979961 | biostudies-literature

Monophosphoryl lipid A-adjuvanted nucleoprotein-neuraminidase nanoparticles improve immune protection against divergent influenza viruses.

Project description:Universal influenza vaccines are urgently needed to prevent recurrent influenza epidemics and inevitable pandemics. We generated double-layered protein nanoparticles incorporating two conserved influenza antigens-nucleoprotein and neuraminidase-through a two-step desolvation-crosslinking method. These protein nanoparticles displayed immunostimulatory properties to antigen-presenting cells by promoting inflammatory cytokine (IL-6 and TNF-α) secretion from JAWS II dendric cells. The nanoparticle immunization induced significant antigen-specific humoral and cellular responses, including antigen-binding and neutralizing antibodies, antibody- and cytokine (IFN-γ and IL-4)-secreting cells, and NP147-155 tetramer-specific cytotoxic T lymphocyte (CTL) responses. Co-administration of monophosphoryl lipid A (MPLA, a toll-like receptor 4 agonist) with the protein nanoparticles further improved immune responses and conferred heterologous and heterosubtypic influenza protection. The MPLA-adjuvanted nanoparticles reduced lung inflammation post-infection. The results demonstrated that the combination of MPLA and conserved protein nanoparticles could be developed into an improved universal influenza vaccine strategy.

| S-EPMC9756393 | biostudies-literature

Stable incorporation of GM-CSF into dissolvable microneedle patch improves skin vaccination against influenza.

Project description:The widely used influenza subunit vaccine would benefit from increased protection rates in vulnerable populations. Skin immunization by microneedle (MN) patch can increase vaccine immunogenicity, as well as increase vaccination coverage due to simplified administration. To further increase immunogenicity, we used granulocyte-macrophage colony stimulating factor (GM-CSF), an immunomodulatory cytokine already approved for skin cancer therapy and cancer support treatment. GM-CSF has been shown to be upregulated in skin following MN insertion. The GM-CSF-adjuvanted vaccine induced robust and long-lived antibody responses cross-reactive to homosubtypic and heterosubtypic influenza viruses. Addition of GM-CSF resulted in increased memory B cell persistence relative to groups given influenza vaccine alone and led to rapid lung viral clearance following lethal infection with homologous virus in the mouse model. Here we demonstrate that successful incorporation of the thermolabile cytokine GM-CSF into MN resulted in improved vaccine-induced protective immunity holding promise as a novel approach to improved influenza vaccination. To our knowledge, this is the first successful incorporation of a cytokine adjuvant into dissolvable MNs, thus advancing and diversifying the rapidly developing field of MN vaccination technology.

| S-EPMC5967648 | biostudies-literature

Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses.

Project description:Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.

| S-EPMC5783933 | biostudies-literature

Self-Assembly M2e-Based Peptide Nanovaccine Confers Broad Protection Against Influenza Viruses.

Project description:The extracellular domain of influenza M2 protein (M2e) is highly conserved and is a promising target for development of universal influenza vaccines. Here, we synthesized a peptide vaccine consisting of M2e epitope linked to a fibrillizing peptide, which could self-assemble into nanoparticle in physiological salt solutions. When administrated into mice without additional adjuvant, the influenza A M2e epitope-bearing nanoparticles induced antibodies against M2e of different influenza subtypes. Comparing with other M2e-based vaccine, these M2e nanoparticles did not induce immune response against the fibrillizing peptide, demonstrating minimal immunogenicity of vaccine carrier. Furthermore, vaccination with M2e-based nanoparticles did not only protect mice against homologous challenge of influenza PR8 H1N1 virus, but also provide protection against heterologous challenge of highly pathogenic avian influenza H7N9 virus. These results indicated that M2e-based self-assembled nanoparticle vaccine is safe and can elicit cross-protection, therefore is a promising candidate of universal influenza vaccines.

| S-EPMC7457018 | biostudies-literature

Universal protection against influenza viruses by multi-subtype neuraminidase and M2 ectodomain virus-like particle.

Project description:Annual influenza vaccination is recommended to update the variable hemagglutinin antigens. Here, we first designed a virus-like particle (VLP) displaying consensus multi-neuraminidase (NA) subtypes (cN1, cN2, B cNA) and M2 ectodomain (M2e) tandem repeat (m-cNA-M2e VLP). Vaccination of mice with m-cNA-M2e VLP induced broad NA inhibition (NAI), and M2e antibodies as well as interferon-gamma secreting T cell responses. Mice vaccinated with m-cNA-M2e VLP were protected against influenza A (H1N1, H5N1, H3N2, H9N2, H7N9) and influenza B (Yamagata and Victoria lineage) viruses containing substantial antigenic variations. Protective immune contributors include cellular and humoral immunity as well as antibody-dependent cellular cytotoxicity. Furthermore, comparable cross protection by m-cNA-M2e VLP vaccination was induced in aged mice. This study supports a novel strategy of developing a universal vaccine against influenza A and B viruses potentially in both young and aged populations by inducing multi-NA subtype and M2e immunity with a single VLP entity.

| S-EPMC9409530 | 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