Nanoparticles for mucosal vaccine delivery
Ontology highlight
ABSTRACT:
SUBMITTER: Thakur A
PROVIDER: S-EPMC7329122 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:The years 2020 and 2021 have witnessed a COVID-19 pandemic caused by the SARS-CoV-2 virus. However, these years have also witnessed certain remarkable scientific achievements. Researchers across the globe have been trying extremely hard and accomplished in bringing vaccines a great variety of COVID-19 vaccines. Though the route of administration for the majority of these vaccines has been the intramuscular route (invasive), some laboratories are developing formulations intended for transmucosal and transcutaneous (non-invasive) administration, which are in the early phases of pre-clinical and clinical development. This short report discusses these unconventional formulations against COVID-19, in brief, to stress the importance of research in the field of drug delivery.
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Project description:Hepatitis E virus is a small, nonenveloped RNA virus that is feco-orally transmitted and causes viral hepatitis in humans. A virus-like particle (VLP) expressed and purified from insect cells shares several properties with the virion but can be manipulated quite extensively through genetic engineering or chemical modification. This has exciting implications for exploiting the VLP as a nanocarrier for foreign epitopes or encapsulated deliverables. By exhaustively studying the structure of the virus, we have been successful in designing and synthesizing chimerized VLPs that either carry foreign epitopes, are capable of encapsulating foreign DNA, or both. Preliminary studies show that these particles provide specific and strong immune responses in mice when orally delivered. To appreciate the full potential of HEV VLPs, we have highlighted various properties of the virus with a strong focus on the VLP structure and the key features that make it suitable for oral delivery.
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Project description:ObjectiveMucosal immunization was an effective defender against pathogens. Nasal vaccines could activate both systemic and mucosal immunity to trigger protective immune responses. However, due to the weak immunogenicity of nasal vaccines and the lack of appropriate antigen carriers, very few nasal vaccines have been clinically approved for human use, which was a major barrier to the development of nasal vaccines. Plant-derived adjuvants are promising candidates for vaccine delivery systems due to their relatively safe immunogenic properties. In particular, the distinctive structure of pollen was beneficial to the stability and retention of antigen in the nasal mucosa.MethodsHerein, a novel wild-type chrysanthemum sporopollenin vaccine delivery system loaded with a w/o/w emulsion containing squalane and protein antigen was fabricated. The unique internal cavities and the rigid external walls within the sporopollenin skeleton construction could preserve and stabilize the inner proteins. The external morphological characteristics were suitable for nasal mucosal administration with high adhesion and retention.ResultsSecretory IgA antibodies in the nasal mucosa can be induced by the w/o/w emulsion with the chrysanthemum sporopollenin vaccine delivery system. Moreover, the nasal adjuvants produce a stronger humoral response (IgA and IgG) compared to squalene emulsion adjuvant. Mucosal adjuvant benefited primarily from prolongation of antigens in the nasal cavity, improvement of antigen penetration in the submucosa and promotion of CD8+ T cells in spleen.DisccusionBased on effective delivering both the adjuvant and the antigen, the increase of protein antigen stability and the realization of mucosal retention, the chrysanthemum sporopollenin vaccine delivery system has the potential to be a promising adjuvant platform. This work provide a novel idea for the fabrication of protein-mucosal delivery vaccine.
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Project description:Immunity against respiratory pathogens is often short-term, and, consequently, there is an unmet need for the effective prevention of such infections. One such infectious disease is coronavirus disease 19 (COVID-19), which is caused by the novel Beta coronavirus SARS-CoV-2 that emerged around the end of 2019. The World Health Organization declared the illness a pandemic on 11 March 2020, and since then it has killed or sickened millions of people globally. The development of COVID-19 systemic vaccines, which impressively led to a significant reduction in disease severity, hospitalization, and mortality, contained the pandemic's expansion. However, these vaccines have not been able to stop the virus from spreading because of the restricted development of mucosal immunity. As a result, breakthrough infections have frequently occurred, and new strains of the virus have been emerging. Furthermore, SARS-CoV-2 will likely continue to circulate and, like the influenza virus, co-exist with humans. The upper respiratory tract and nasal cavity are the primary sites of SARS-CoV-2 infection and, thus, a mucosal/nasal vaccination to induce a mucosal response and stop the virus' transmission is warranted. In this review, we present the status of the systemic vaccines, both the approved mucosal vaccines and those under evaluation in clinical trials. Furthermore, we present our approach of a B-cell peptide-based vaccination applied by a prime-boost schedule to elicit both systemic and mucosal immunity.
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Project description:Since besides mucosal adaptive immunity, respiratory delivery of AdHu5Ag85A vaccine in experimental animals induced a trained phenotype in airway macrophages, we examined whether aerosol vaccination with AdHu5Ag85A could also alter the immune property of human alveolar macrophages (AM). To this end, we elected to examine the transcriptomics of BALF cells obtained from 5 participants before (wk0) and after (wk8) 1x106PFU AdHu5Ag85A aerosol vaccination. Before RNA isolation, the cells, upon revival from frozen stock, were enriched for AM and cultured with or without stimulation with M.tb lysates and transcriptionally profiled by RNAseq analysis. Principal component analysis (PCA) revealed that unstimulated (US) and stimulated (S) AM populations were separated away from each other. We then identified the differentially expressed genes (DEGs) by comparing wk0- and wk8-stimulated AM with respective unstimulated AM. By this pairwise analysis, we identified 194 and 426 genes uniquely upregulated and downregulated, respectively, in stimulated AM from aerosol vaccinated participants. The uniquely up-regulated genes in stimulated wk8 aerosol AM showed enrichment in a number of biological processes including response to anoxia (OXTR, CTGF), inflammatory response to antigenic stimuli (IL2RA, IL1B, IL20RB), tyrosine phosphorylation of STAT protein (IFNG, F2R, OSM), regulation of IL-10 production (CD83, IRF4, IL20RB, IDO1), response to IL-1 (RIPK2, SRC, IRAK2, IL1R1, XYLT1, RELA) and histone demethylation (KDM6B, KDM5B, KDM1A, KDM7A, JMJD6). In comparison, the uniquely down-regulated genes in wk8 aerosol AM did not appear significantly enriched for any biological processes. These data suggest that aerosol vaccination leads to persisting transcriptional changes in airway-resident alveolar macrophages poised for defense responses.
2022-02-23 | GSE190850 | GEO
Project description:Targeted delivery of antigens to immune cells using micro/nanocarriers may serve as a therapeutic application for vaccination. However, synthetic carriers have potential drawbacks including cytotoxicity, low encapsulation efficiency of antigen, and lack of a morphological design, which limit the translation of the delivery system to clinical use. Here, we report a carrier-free and three-dimensional (3D)-shape-designed antigen nanoparticle by multiphoton lithography-based 3D-printing. This simple, versatile 3D-printing approach provides freedom for the precise design of particle shapes with a nanoscale resolution. Importantly, shape-designed antigen nanoparticles with distinct aspect ratios show shape-dependent immune responses. The 3D-printing approach for the rational design of nanomaterials with increasing safety, complexity, and efficacy offers an emerging platform to develop vaccine delivery systems and mechanistic understanding.
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Project description:mRNA vaccines can be translated into protein antigens, in vivo, to effectively induce humoral and cellular immunity against these proteins. While current mRNA vaccines have generated potent immune responses, the need for ultracold storage conditions (- 80 °C) and healthcare professionals to administer the vaccine through the parenteral route has somewhat limited their distribution in rural areas and developing countries. Overcoming these challenges stands to transform future deployment of mRNA vaccines. In this study, we developed an mRNA vaccine that can trigger a systemic immune response through administration via the gastrointestinal (GI) tract and is stable at 4 °C. A library of cationic branched poly(β-amino ester) (PBAE) polymers was synthesized and characterized, from which a polymer with high intracellular mRNA delivery efficiency and immune stimulation capacity was down-selected. mRNA vaccines made with the lead polymer-elicited cellular and humoral immunity in mice. Furthermore, lyophilization conditions of the formulation were optimized to enable storage under refrigeration. Our results suggest that PBAE nanoparticles are potent mRNA delivery platforms that can elicit B cell and T cell activation, including antigen-specific cellular and humoral responses. This system can serve as an easily administrable, potent oral mRNA vaccine.
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Project description:The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses.Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner lower lip and dorsal surface of the tongue of rabbits. Histology was used to confirm microneedle insertion, and systemic and mucosal immune responses were characterized by measuring antigen-specific immunoglobulin G (IgG) in serum and immunoglobulin A (IgA) in saliva, respectively.Histological evaluation of tissues shows that coated microneedles can penetrate the lip and tongue to deliver coatings. Using ovalbumin as a model antigen it was found that the lip and the tongue are equally immunogenic sites for vaccination. Importantly, both sites also induced a significant (p?<?0.05) secretory IgA in saliva compared to pre-immune saliva. Microneedle-based oral cavity vaccination was also compared to the intramuscular route using two HIV antigens, a virus-like particle and a DNA vaccine. Microneedle-based delivery to the oral cavity and the intramuscular route exhibited similar (p?>?0.05) yet significant (p?<?0.05) levels of antigen-specific IgG in serum. However, only the microneedle-based oral cavity vaccination group stimulated a significantly higher (p?<?0.05) antigen-specific IgA response in saliva, but not intramuscular injection.In conclusion, this study provides a novel method using microneedles to induce systemic IgG and secretory IgA in saliva, and could offer a versatile technique for oral mucosal vaccination.
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Project description:A novel oral protein delivery system with enhanced intestinal penetration and improved antigen stability based on chitosan (CS) nanoparticles and antigen-cyclodextrin (CD) inclusion complex was prepared by a precipitation/coacervation method. Ovalbumin (OVA) as a model antigen was firstly encapsulated by cyclodextrin, either ?-cyclodextrin (?-CD) or carboxymethyl-hydroxypropyl-?-cyclodextrin (CM-HP-?-CD) and formed OVA-CD inclusion complexes, which were then loaded to chitosan nanoparticles to form OVA loaded ?-CD/CS or CM-HP-?-CD/CS nanoparticles with uniform particle size (836.3 and 779.2?nm, respectively) and improved OVA loading efficiency (27.6% and 20.4%, respectively). In vitro drug release studies mimicking oral delivery condition of OVA loaded CD/CS nanoparticles showed low initial releases at pH 1.2 for 2?h less than 3.0% and a delayed release which was below to 30% at pH 6.8 for further 72?h. More importantly, after oral administration of OVA loaded ?-CD/CS nanoparticles to Balb/c mice, OVA-specific sIgA levels in jejunum of OVA loaded ?-CD/CS nanoparticles were 3.6-fold and 1.9-fold higher than that of OVA solution and OVA loaded chitosan nanoparticles, respectively. In vivo evaluation results showed that OVA loaded CD/CS nanoparticles could enhance its efficacy for inducing intestinal mucosal immune response. In conclusion, our data suggested that CD/CS nanoparticles could serve as a promising antigen-delivery system for oral vaccination.
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Project description:Effective vaccines for human immunodeficiency virus type 1 (HIV-1) will likely need to stimulate protective immunity in the intestinal mucosa, where HIV-1 infection causes severe CD4(+) T-cell depletion. While replication-competent recombinant adenovirus (rAd) vectors can stimulate adenovirus-specific mucosal immunity after replication, oral delivery of replication-defective rAd vectors encoding specific immunogens has proven challenging. In this study, we have systematically identified barriers to effective gut delivery of rAd vectors and identified sites and strategies to induce potent cellular and humoral immunity. Vector-mediated gene transfer by rAd5 was susceptible to low-pH buffer, gastric and pancreatic proteases, and extracellular mucins. Using ex vivo organ explants, we found that transduction with rAd5 was highest in the ileum and colon among all intestinal segments. Transgene expression was 100-fold higher after direct surgical introduction into the ileum than after oral gavage, with rAd5 showing greater potency than the rAd35 or the rAd41 vector. A single immunization of rAd5 encoding HIV-1 gp140B to the ileum stimulated potent CD8(+) T-cell responses in the intestinal and systemic compartments, and these responses were further enhanced by intramuscular rAd5 boosting. These studies suggest that induction of primary immune responses by rAd5 gut immunization and subsequent systemic boosting elicits potent antigen-specific gut mucosal responses.
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