RESUMO
Disease outbreaks are a major impediment to aquaculture production, and vaccines are integral for disease management. Vaccines can be expensive, vary in effectiveness, and come with adjuvant-induced adverse effects, causing fish welfare issues and negative economic impacts. Three-dimensional biopolymer hydrogels are an appealing new technology for vaccine delivery in aquaculture, with the potential for controlled release of multiple immunomodulators and antigens simultaneously, action as local depots, and tunable surface properties. This research examined the intraperitoneal implantation of a cross-linked TEMPO cellulose nanofiber (TOCNF) hydrogel formulated with a Vibrio anguillarum bacterin in Atlantic salmon with macroscopic and microscopic monitoring to 600-degree days post-implantation. Results demonstrated a modified passive integrated transponder tagging (PITT) device allowed for implantation of the hydrogel. However, the Atlantic salmon implanted with TOCNF hydrogels exhibited a significant foreign body response (FBR) compared to sham-injected negative controls. The FBR was characterized by gross and microscopic external and visceral proliferative lesions, granulomas, adhesions, and fibrosis surrounding the hydrogel using Speilberg scoring of the peritoneum and histopathology of the body wall and coelom. Acutely, gross monitoring displayed rapid coagulation of blood in response to the implantation wound with development of fibrinous adhesions surrounding the hydrogel by 72 h post-implantation consistent with early stage FBR. While these results were undesirable for aquaculture vaccines, this work informs on the innate immune response to an implanted biopolymer hydrogel in Atlantic salmon and directs future research using cellulose nanomaterial formulations in Atlantic salmon for a new generation of aquaculture vaccine technology.
Assuntos
Celulose Oxidada , Doenças dos Peixes , Nanofibras , Salmo salar , Animais , Hidrogéis , Antígenos , Adjuvantes Imunológicos , Vacinas Bacterianas , Celulose , AquiculturaRESUMO
Aeromonas hydrophila, an opportunistic warm water pathogen, has always been a threat to aquaculture, leading to substantial economic losses. Vaccination of the cultured fish would effectively prevent Aeromoniasis, and recent advancements in nanotechnology show promise for efficacious vaccines. Oral delivery would be the most practical and convenient method of vaccine delivery in a grow-out pond. This study studied the immunogenicity and protective efficacy of a nanoparticle-loaded outer membrane protein A from A. hydrophila in the zebrafish model. The protein was over-expressed, purified, and encapsulated using poly lactic-co-glycolic acid (PLGA) nanoparticles via the double emulsion method. The PLGA nanoparticles loaded with recombinant OmpA (rOmpA) exhibited a size of 295 ± 15.1 nm, an encapsulation efficiency of 72.52%, and a polydispersity index of 0.292 ± 0.07. Scanning electron microscopy confirmed the spherical and isolated nature of the PLGA-rOmpA nanoparticles. The protective efficacy in A. hydrophila-infected zebrafish after oral administration of the nanovaccine resulted in relative percentage survival of 77.7. Gene expression studies showed significant upregulation of immune genes in the vaccinated fish. The results demonstrate the usefulness of oral administration of nanovaccine-loaded rOmpA as a potential vaccine since it induced a robust immune response and conferred adequate protection against A. hydrophila in zebrafish, Danio rerio.
Assuntos
Aeromonas hydrophila , Proteínas da Membrana Bacteriana Externa , Vacinas Bacterianas , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Nanopartículas , Proteínas Recombinantes , Peixe-Zebra , Animais , Peixe-Zebra/imunologia , Aeromonas hydrophila/imunologia , Aeromonas hydrophila/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/genética , Administração Oral , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Vacinação , NanovacinasRESUMO
Red tilapia (Oreochromis sp.), one of the important freshwater fish species in fish farming in Thailand, has for long been suffering from a serious bacterial disease named epizootic ulcerative syndrome and hemorrhagic septicemia. The disease is mainly caused by Aeromonas veronii. Vaccine is proposed to be a major impact tool for sustainable control and prevention strategies. Vaccination by immersion has many benefits over injection. However, the conventional immersion method suffers from a low potency due to the inefficient uptake of antigens across mucosal tissue. Here, we developed a chitosan-polymer based nanovaccine together with an efficient delivery vehicle to enhance the immunogenicity of immersion vaccination, increasing bioavailability and inducing local immune responses during transit to mucosal inductive immune sites. The physiochemical properties of nanovaccine, which was modified on surface particle by using a mucoadhesive polymer, were assessed for size, zeta potential, and particle distribution. Our study demonstrated by SEM image and microscopic fluorescence image that nanovaccine greatly increased the binding and penetrating ability into gills when compared with formalin killed vaccine. The nano-sized particles were well dispersed in water and trapped in core nanoparticle as confirmed by TEM image. The efficacy of vaccine was performed by immersion challenge with virulent A.veronii after 30 days post vaccination in tilapia. The result revealed a high level of mortality in the control, empty-polymeric nanovaccine and formalin killed bacterin vaccine groups. A high relative percentage survival (RPS) of vaccinated fish was noted with chitosan-polymer based nanovaccine. Our studies indicated that this chitosan-polymer based nanovaccine derived from cell fragments and supernatant was the improved version of the conventional formalin killed vaccine. The chitosan polymer based particle could increase the efficacy of nanovaccine toward the target mucosal membrane and enhance protection against A. veronii infection in red tilapia.
Assuntos
Quitosana , Ciclídeos , Doenças dos Peixes , Tilápia , Aeromonas veronii , Animais , Vacinas Bacterianas , Formaldeído , Imersão , Polímeros , Vacinas de Produtos Inativados , ÁguaRESUMO
Bacterial membrane vesicles (MVs) are particles secreted by bacteria with diameter of 20-400â¯nm. The pathogen-associated molecular patterns (PAMPs) present on the surface of MVs are capable of activating human immune system, leading to non-specific immune response and specific immune response. Due to the immunostimulatory properties and proteoliposome nanostructures, MVs have been increasingly explored as vaccines or delivery systems for the prevention and treatment of bacterial infections. Herein, the recent progresses of MVs for antibacterial applications are reviewed to provide an overview of MVs vaccines and MVs-related delivery systems. In addition, the safety issues of bacterial MVs are discussed to demonstrate their potential for clinical translation. In the end of this review, the challenges of bacterial MVs as vaccines and delivery systems for clinical applications are highlighted with the purpose of predicting future research directions in this field.
Assuntos
Bactérias , Infecções Bacterianas , Proteínas de Bactérias , Vacinas Bacterianas , Membrana Celular , Nanoestruturas , Bactérias/química , Bactérias/imunologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/uso terapêutico , Vacinas Bacterianas/química , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Membrana Celular/química , Membrana Celular/imunologia , Humanos , Lipossomos , Nanoestruturas/química , Nanoestruturas/uso terapêuticoRESUMO
Leptospirosis is a debilitating infectious disease that detrimentally affects both animals and humans; therefore, disease prevention has become a high priority to avoid high incidence rates of disease in the herd and break the transmission cycle to humans. Thus, there remains an important unmet need for a prophylactic vaccine that can provide long-term immunity against leptospirosis in cattle. Herein, a novel vaccine formulation was developed where poly(diaminosulfide) polymer was employed to fabricate microparticles encapsulating the antigen of Leptospira borgpetersenii serovar Hardjo strain HB15B203 (L203-PNSN). A prime-boost vaccination with a L203-PNSN microparticle formulation increased the population of L203-specific CD3+ T cells and CD21+ B cells to levels that were significantly higher than those of cattle vaccinated with L203-AlOH or the vehicle control (empty PNSN microparticles and blank AlOH). In addition, L203-PNSN was demonstrated to stimulate durable humoral immune responses as evidenced by the increases in the antibody serum titers following the vaccination. It was also found that cattle vaccinated with L203-PNSN produced higher macroscopic agglutinating titers than cattle in other groups. Thus, it can be concluded that L203-PNSN is a novel first-in-class microparticle-based Leptospira vaccine that represents a powerful platform with the potential to serve as a prophylactic vaccine against leptospiral infection in cattle.
Assuntos
Antígenos de Bactérias/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Leptospira/imunologia , Leptospirose/prevenção & controle , Microplásticos/química , Animais , Vacinas Bacterianas/imunologia , Bovinos , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/prevenção & controle , Sistemas de Liberação de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática , Imunidade Humoral , Imunização Secundária , Leptospirose/imunologia , Leptospirose/veterinária , Masculino , Microplásticos/síntese química , Polímeros/química , Linfócitos T/imunologiaRESUMO
Antigen-specific CD8+ T-lymphocytes (cytotoxic T-lymphocytes: CTL), as well as CD4+ T-lymphocytes (helper T-lymphocytes: Th), simultaneously play an important role in the elimination of intracellular bacteria such as Mycobacterium tuberculosis and Listeria monocytogenes. Administration of T-cell epitope short peptide needs large numbers of peptides for effective vaccination due to its easily degradable nature in vivo. In this respect, biocompatible and biodegradable microparticles combined with CTL/Th-hybrid epitope long peptide (long peptide) have been used to diminish the degradation of loaded peptide. The aim of this study is to develop a novel T cell-oriented vaccine against intracellular bacteria that is composed of long peptide and poly (lactic-co-glycolic acid) (PLGA) microparticles. Mouse bone marrow-derived dendritic cells (BMDCs) were loaded with L. monocytogenes listeriolysin O (LLO)-derived or ovalbumin (OVA)-derived long peptide/PLGA or other comparative antigens. The antigen-loaded BMDCs were injected subcutaneously into the flank of mice twice, and then, the spleens were collected and lymphocyte proliferation and interferon-γ production were evaluated. The median diameter of the PLGA spheres was 1.38 µm. Both LLO- and OVA-long peptide/PLGA showed significantly more robust CTL and Th proliferations with higher interferon-γ production than the long peptide alone or CTL and Th short peptides/PLGA vaccination. Furthermore, the LLO-long peptide/PLGA vaccination showed a significantly lower bacterial burden in spleens compared with the long peptide alone or the CTL and Th short peptides/PLGA vaccination after the challenge of lethal amounts of L. monocytogenes. These results suggest that the novel vaccine taking advantages of CTL/Th-hybrid epitope long peptide and PLGA microparticle is effective for protection against intracellular bacteria.
Assuntos
Vacinas Bacterianas/imunologia , Células Dendríticas/transplante , Epitopos de Linfócito T/imunologia , Listeria monocytogenes/imunologia , Listeriose/prevenção & controle , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/imunologia , Animais , Toxinas Bacterianas/imunologia , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Células Cultivadas , Células Dendríticas/imunologia , Feminino , Proteínas de Choque Térmico/imunologia , Proteínas Hemolisinas/imunologia , Interferon gama/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Linfócitos T Citotóxicos/imunologia , VacinaçãoRESUMO
BACKGROUND: The global prevalence of economic primary infection of poultry by H9N2 virus, including the Lineage A, panzootic group ME1, and associated with secondary infection by Mycoplasma gallisepticum (MG), is alarming to the sustainability of the poultry sector. This research evaluated in broilers the immunity and protection induced by aerosolization of liposomal nanoparticles vaccine, encapsulating antigens of H9N2 virus and MG, with or without the incorporation of Echinacea extract (EE) immuno-stimulant. Six different treatments (TRTs) of broilers were included in the experimental design, with three replicate pens/TRT and stocking of 20 day-old birds/replicate. RESULTS: The tracheobronchial washings of birds subjected to aerosolization of liposomal nanoparticles, encapsulating antigens of H9N2 and MG and EE had the highest significant mean levels of each of IgA and IgG specific to H9N2 and MG, associated with lowest tracheal MG colonization, tracheal H9N2 recovery, tracheal histopathologic lesions, mortality, and best performance in body weight and feed conversion compared to all other challenged birds allocated to different treatments (P < 0.05). However, the control broilers, free from challenge with MG and H9N2, had the lowest mortality and tracheal lesions, and the highest production performance. CONCLUSION: The aerosolization of liposomal nanoparticles, encapsulating antigens of H9N2 and MG and EE resulted in enough local immunity for protection of broilers against infection, and in attaining the highest production performance in challenged birds. The potential implication of vaccinating with safe killed nanoparticle vaccines is of utmost importance to the global poultry sector.
Assuntos
Vacinas Bacterianas/imunologia , Galinhas , Vírus da Influenza A Subtipo H9N2/imunologia , Vacinas contra Influenza/imunologia , Mycoplasma gallisepticum/imunologia , Nanopartículas/administração & dosagem , Aerossóis , Animais , Antígenos Virais , Vacinas Bacterianas/administração & dosagem , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Vacinas contra Influenza/administração & dosagem , Influenza Aviária/prevenção & controle , Lipossomos , Infecções por Mycoplasma/prevenção & controle , Infecções por Mycoplasma/veterináriaRESUMO
Dental caries, caused by Streptococcus mutans, is a common infection. Caries vaccine has been under investigation for the last 40 years. Many in vitro and in vivo studies and some human clinical trials have determined many pertinent aspects regarding vaccine development. The virulence determinants of Strep. mutans, such as Ag I/II, responsible for adherence to surfaces, glucosyltransferase, responsible for the production of glucan, and the glucan-binding protein, responsible for the attachment of glucan to surfaces, have been known to elicit an antigen-specific immune response. It is also known that more than one antigen or a functional part of the genome responsible for these virulence determinants provide a better host response compared with the monogenic vaccine or complete genome of a specific antigen. To enhance the host response, the use of adjuvants has been studied and the routes of antigen administration have been investigated. In recent years, some promising vaccines such as pGJA-P/VAX, LT derivative/Pi39-512 , KFD2-rPAc and SBR/GBR-CMV-nirB have been developed and tested in animals. New virulence targets need to be explored. Multicentre collaborative studies and human clinical trials are required and some interest from funders and public health experts should be generated to overcome this hurdle. SIGNIFICANCE AND IMPACT OF THE STUDY: Dental caries is an irreversible, multifactorial opportunistic infection. The treatment is costly, making it a public health problem. Despite many years of promising laboratory research, animal studies and clinical trials, there is no commercially available vaccine today. The research objectives have become more refined from lessons learnt over the years. Multigenic DNA/recombinant vaccines, using the best proved adjuvants with a delivery system for the nasal or sublingual route, should be developed and researched with multicentre collaborative efforts. In addition, new vaccine targets can be identified. To overcome the economic hurdle, funders and public health interest should be stimulated.
Assuntos
Vacinas Bacterianas/imunologia , Cárie Dentária/prevenção & controle , Streptococcus mutans/imunologia , Animais , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/genética , Cárie Dentária/microbiologia , Humanos , Streptococcus mutans/genética , Streptococcus mutans/fisiologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Vacinas de DNA/imunologiaRESUMO
We previously demonstrated that recombinant protein PAc could be administered as an anticaries vaccine. However, the relatively weak immunogenicity of PAc limits its application. In the present study, we investigated the effect of two adjuvant combinations of chitosan plus Pam3CSK4 (chitosan-Pam3CSK4) and of chitosan plus monophosphoryl lipid A (chitosan-MPL) in the immune responses to the PAc protein in vivo and in vitro PAc-chitosan-Pam3CSK4 or PAc-chitosan-MPL promoted significantly higher PAc-specific antibody titers in serum and saliva, inhibited Streptococcus mutans colonization onto the tooth surfaces, and endowed better protection effect with significantly less caries activities than PAc alone. Chitosan-Pam3CSK4 and chitosan-MPL showed no statistically significant differences. In conclusion, our study demonstrated that the chitosan-Pam3CSK4 and chitosan-MPL combinations are promising for anticaries vaccine development.
Assuntos
Vacinas Bacterianas/imunologia , Quitosana/farmacologia , Cárie Dentária/prevenção & controle , Lipídeo A/análogos & derivados , Lipopeptídeos/farmacologia , Streptococcus mutans/imunologia , Adjuvantes Imunológicos , Animais , Cárie Dentária/microbiologia , Feminino , Imunogenicidade da Vacina/imunologia , Imunoglobulina A Secretora/análise , Lipídeo A/imunologia , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas NLR/agonistas , Streptococcus mutans/patogenicidade , Receptores Toll-Like/agonistas , Vacinas Sintéticas/imunologia , Fatores de Virulência/imunologiaRESUMO
Acinetobacter baumannii (A baumannii) is an emerging nosocomial pathogenic bacterium which leads to hospital infections. The increase in drug-resistant A baumannii strains makes it difficult to control by using common antibiotics. The development of effective vaccines is an alternative means to avoid A baumannii infections. In the present study, Balb/c mice were inoculated intratracheally with 30 µg of OmpK/Omp22 fusion protein alone or OmpK/Omp22 formulated with MF59 adjuvant. After two times of boosting at day 14 and 21, the antigen-specific antibody levels and the protective immunity against A baumannii challenge were evaluated. The results showed that the OmpK/Omp22 formulated with MF59 immunized mice produced much higher level of antigen-specific antibodies compared to mice immunized with OmpK/Omp22 alone (P < 0.01). Mice immunized with 30 µg of OmpK/Omp22 formulated with MF59 also provided more potent protection post-challenge, which showed lower bacterial loads in the blood and lung tissue, lower level of blood inflammatory cytokines and higher survival rate (83.3%) than mice immunized with OmpK/Omp22 alone (P < 0.001). In conclusion, this study demonstrated that OmpK/Omp22 fusion protein adjuvanted with MF59 induced superior immune response and better protection than OmpK/Omp22 alone through intratracheal inoculation in mice.
Assuntos
Infecções por Acinetobacter/imunologia , Acinetobacter baumannii/fisiologia , Adjuvantes Imunológicos , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Proteínas Recombinantes de Fusão/imunologia , Esqualeno/imunologia , Animais , Carga Bacteriana , Infecção Hospitalar , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Polissorbatos , Traqueia/metabolismo , VacinaçãoRESUMO
Two monovalent vaccines against pasteurellosis were developed and tested for efficacy using a previously established bath challenge model. High levels of specific antibodies were detected following vaccination. While the vaccine efficacy trial indicated that some level of protection was obtained, high mortality was still observed. qPCR analysis of head kidney tissues from surviving fish post challenge showed no difference in bacterial numbers in vaccinated and non-vaccinated fish. Clinical symptoms observed in moribund and diseased fish included white spots on the skin and around the eyes, frayed fins and redness around the mouth and fin bases. Despite production of specific antibodies, the protection against experimental challenge was relatively weak. A reason for this could potentially be that the specific antibodies produced are not alone enough to provide complete protection against pasteurellosis in lumpsuckers. Confocal and scanning electron microscopy of head kidney leucocytes exposed to Pasteurella sp. in vitro gave indications of the interactions between the pathogen and leucocytes. The results indicate that parts of the immune system other than humoral antibodies could be important for protection against pasteurellosis. Our combined results highlight the need for further work on host-pathogen interaction between Pasteurella sp. and lumpsuckers.
Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/imunologia , Doenças dos Peixes/imunologia , Infecções por Pasteurella/veterinária , Perciformes/imunologia , Imunidade Adaptativa , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/administração & dosagem , Doenças dos Peixes/microbiologia , Doenças dos Peixes/prevenção & controle , Rim Cefálico/imunologia , Rim Cefálico/microbiologia , Pasteurella , Infecções por Pasteurella/prevenção & controle , Perciformes/microbiologia , VacinaçãoRESUMO
Vaccination is the most effective approach for prevention of infectious diseases in aquaculture. Although immersion vaccination is more applicable compared to in-feed/oral administration and injection, this method suffers from low potency as the efficiency of uptake of antigens through mucosal membranes is limited. In this study, we have successfully developed a mucoadhesive vaccine delivery system to enhance the efficacy of direct immersion vaccination against Flavobacterium columnare, the causative agent of columnaris disease in red tilapia. A formalin-killed negatively charged, bacterial cell suspension was used to prepare a mucoadhesive vaccine by electrostatic coating with positively charged chitosan. Our results demonstrate that the chitosan-complexed vaccine greatly increases its mucoadhesiveness, thus increasing the chances of vaccine uptake by the gill mucosa and improving the protection obtained against columnaris infection. The surface charge of the chitosan-complexed vaccine was altered from anionic to cationic after chitosan modification. Tilapia were vaccinated with the prepared chitosan-complexed vaccine by immersion. The challenge test was then carried out 30 and 60 days post vaccination, which resulted in a high level of mortalities in the non-vaccinated and uncomplexed vaccine groups. A high relative percentage survival (RPS) of vaccinated fish was noted with the mucoadhesive vaccine. Our results indicated that the naked vaccine failed to protect the fish from columnaris infection, which is consistent with the mucoadhesive assays performed during the study showing that the naked vaccine was unable to bind to mucosal surfaces. This system is therefore an effective method for immersion vaccination in order to deliver the antigen preparation to the mucosal surface membrane of the fish.
Assuntos
Vacinas Bacterianas/uso terapêutico , Doenças dos Peixes/prevenção & controle , Infecções por Flavobacteriaceae/veterinária , Polímeros/química , Tilápia/imunologia , Vacinação/métodos , Adesivos/química , Animais , Aquicultura , Vacinas Bacterianas/química , Quitosana/química , Infecções por Flavobacteriaceae/prevenção & controle , Flavobacterium , Brânquias/imunologia , Imersão , Mucosa/metabolismo , Eletricidade Estática , Propriedades de Superfície , Tilápia/microbiologia , Vacinas de Produtos Inativados/química , Vacinas de Produtos Inativados/uso terapêuticoRESUMO
INTRODUCTION: Periodontal diseases (PD) are complex oral inflammatory diseases initiated by keystone bacteria such as Porphyromonas gingivalis. A vaccine for PD is desirable as clinical treatment involves protracted maintenance strategies aimed to retain dentition. Although prior immunization approaches targeting P. gingivalis have reported variable success in limiting facets of disease such as oral bone loss, it remains that a vaccine for this disease may be attainable. AIM: To investigate cell-free protein synthesis (CFPS) as a platform to produce vaccinable targets suitable for efficacy testing in a P. gingivalis-induced murine oral bone loss model. MATERIALS AND METHODS: Recombinantly generated P. gingivalis minor fimbriae protein (Mfa1), RgpA gingipain hemagglutinin domain 1 (HA1), and RgpA gingipain hemagglutinin domain 2 (HA2) were combined in equivalent doses in adjuvants and injected intramuscularly to immunize mice. Serum levels of protein-specific antibody were measured by ELISA, and oral bone levels were defined by morphometrics. RESULTS: Recombinantly generated P. gingivalis proteins possessed high fidelity to predicted size and elicited protein-specific IgG following immunization. Importantly, immunization with the vaccine cocktail protected from P. gingivalis elicited oral bone loss. CONCLUSION: These data verify the utility of the CFPS technology to synthesize proteins that have the capacity to serve as novel vaccines.
Assuntos
Perda do Osso Alveolar , Infecções por Bacteroidaceae , Adesinas Bacterianas , Animais , Anticorpos Antibacterianos , Vacinas Bacterianas , Cisteína Endopeptidases , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Porphyromonas gingivalisRESUMO
Cell membrane engineering, including live cell membrane bioconjugation and cell membrane-derived nanomaterials is a highly promising strategy to modulate immune responses for treating diseases. Many cell membrane engineering methods have potential for translation for human clinical use in the near future. In this Topical Review, we summarize the cell membrane conjugation strategies that have been investigated for cancer immunotherapy, the prevention of immune rejection to donor cells and tissues, and the induction of antigen-specific tolerance in autoimmune diseases. Additionally, cell membrane-derived or membrane-coated nanomaterials are an emerging class of nanomaterials that is attracting significant attention in the field of nanomedicine. Some of these nanomaterials have been employed to elicit immune responses against cancer, toxins, and bacteria, although their application in establishing immune tolerance has not been explored. In addition to discussing potential problems, we provide our perspectives for promising future directions.
Assuntos
Materiais Biocompatíveis/química , Membrana Celular/química , Imunoterapia/métodos , Nanomedicina/métodos , Nanoestruturas/química , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Vacinas Bacterianas/química , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Membrana Celular/imunologia , Técnicas de Química Sintética/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Tolerância Imunológica , Nanoestruturas/uso terapêutico , Neoplasias/imunologia , Neoplasias/terapiaRESUMO
The immunogenicity of oral subunit vaccines is poor partly as a result of the harsh milieu of the gastrointestinal (GI) tract. For some pathogens that restrictedly inhabit the GI tract, a vaccine that works in situ may provide more potent protection than vaccines that operate parenterally. Yet, no appropriate delivery system is available for oral subunit vaccines. In this study, we designed HP55/poly( n-butylcyanoacrylate) (PBCA) nanoparticles (NPs) to carry Helicobacter pylori ( H. pylori) subunit vaccine CCF for oral administration in a prophylactic mice model. These NPs, which are synthesized using an interfacial polymerization method, protected the CCF antigen not only from the acidic pH in simulated gastric fluid (SGF, pH 1.2) but also from the proteolysis in simulated intestinal fluid (SIF, pH 7.4). Oral vaccination of mice with HP55/PBCA-CCF NPs promoted the production of serum antigen-specific antibodies, mucosal secretory IgA, and proinflammatory cytokines. Moreover, a Th1/Th17 response and augmented lymphocytes were found in the gastric tissue of HP55/PBCA-CCF NP-immunized mice, which might eventually limit H. pylori colonization. Collectively, these results indicate that HP55/PBCA NPs are promising carriers against the severe situation of the GI tract and thereby may be further utilized for other orally administrated vaccines or drugs.
Assuntos
Vacinas Bacterianas/imunologia , Portadores de Fármacos/química , Infecções por Helicobacter/terapia , Imunogenicidade da Vacina , Administração Oral , Animais , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/metabolismo , Cianoacrilatos/química , Modelos Animais de Doenças , Feminino , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Humanos , Imunidade Celular/efeitos dos fármacos , Masculino , Metilcelulose/análogos & derivados , Metilcelulose/química , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Proteólise , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/metabolismoRESUMO
The efficacy of a Eudragit L30D-55 encapsulated vaccine against Lactococcus garvieae and Streptococcus iniae was investigated in rainbow trout. Fish were divided into four groups and fed the different experimental feeds. Groups were: A) fish immunized by Eudragit-coated pellets containing vaccine, B) fish immunized by vaccine-coated pellets without Eudragit, C) fish fed Eudragit-coated pellets without vaccine and D) fish fed pellets without vaccine orEudragit (control group). In groups A and B, the vaccination was conducted for 14 days. Similar to groups A and B, fish of group C were fed 14 days with pellets coated with Eudragit and afterwards they were fed control diet. Serum samples were taken on day 0, 20, 40 and 60 of the experiment. After 60 days, fish were challenged with L. garvieae and S. iniae. In almost all groups, innate immunity components including alternative complement activity, lysozyme activity, bactericidal activity, IgM and total protein showed no significant changes during the 60 days that the experiment lasted. However, the blood respiratory burst activity and lysozyme activity showed a significant increase on day 20 of experiment in groups B and D respectively (Pâ¯<â¯0.05). The relative expression of immune-related genes including IL-6 and IgM genes was higher in vaccinated fish, with the highest expression in those immunized by Eudragit-coated pellets (Group A). In addition, the relative expression of IL-6 and IgM peaked on day 20 but decreased on day 60 in vaccinated groups. The ELISA antibody titer against L. garvieae increased from day 20 and peaked on day 60 of experiment (Pâ¯<â¯0.05). Also, the antibody titer against L. garvieae was higher in fish immunized by Eudragit-coated pellets (Group A) compared to fish of group C and control. After bacterial challenge, a survival percentages of % 85⯱â¯7.07% (challenged with S. iniae) and % 72.21⯱â¯7.8% (challenged with L. garvieae) were observed respectively in groups immunized with pellets coated with Eudragit L30D-55 (Group A), which were higher than survival percentages obtained in other experimental groups (Pâ¯<â¯0.05). The results of the present study demonstrate that the oral administration of Eudragit L30D-55-encapsulated vaccine appropriately protects rainbow trout against Lactococcus garvieae and Streptococcus iniae.
Assuntos
Vacinas Bacterianas/administração & dosagem , Excipientes/administração & dosagem , Metacrilatos/administração & dosagem , Oncorhynchus mykiss/imunologia , Polímeros/administração & dosagem , Vacinas de Produtos Inativados/administração & dosagem , Administração Oral , Animais , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Positivas/prevenção & controle , Imunoglobulina M/genética , Interleucina-6/genética , Lactococcus/imunologia , Streptococcus iniae/imunologiaRESUMO
Streptococcus agalactiae (S. agalactiae) is an important fish pathogen, which has received more attention in the past decade due to the increasing economic losses in the tilapia industry worldwide. As existing effective vaccines of S. agalactiae in fish have obvious disadvantage, to select immunoprotective antigens and package materials would undoubtedly contribute to the development of novel oral vaccines. In the present study, surface immunogenic protein (sip) was selected from the S. agalactiae serovar I a genomes as immunogenic protein in DNA vaccine form with cationic chitosan and biodegradable and biocompatible PLGA. The pcSip plasmid in cationic-PLGA was successfully expressed in tissues of immunized tilapia and the immunogenicity was assessed in tilapia challenge model. A significant increase was observed in the cytokine levels of IL-1ß, TNF-α, CC1, CC2 in spleen and kidney tissues. Furthermore, immunized tilapia conferred different levels of protection against challenge with a lethal dose of highly virulent serovar I a S. agalactiae. Our results indicated that the pcSip plasmid in cationic-PLGA induced high level of antibodies and protection against S. agalactiae infection, could be effective oral DNA vaccine candidates.
Assuntos
Vacinas Bacterianas/imunologia , Doenças dos Peixes/prevenção & controle , Imunidade Inata , Imunogenicidade da Vacina , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/imunologia , Tilápia , Animais , Quitosana/metabolismo , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Genes Bacterianos/imunologia , Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Distribuição Aleatória , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae/genética , Distribuição Tecidual , Vacinas de DNA/imunologiaRESUMO
OBJECTIVE: Following Porphyromonas gingivalis infection in mice, the efficacy of vaccination by recombinant and native RgpA in modulating the early local anti-inflammatory and immune responses and periodontal bone loss were examined. MATERIAL AND METHODS: Using the subcutaneous chamber model, exudates were analyzed for cytokines after treatment with native RgpA and adjuvant (test), or adjuvant and saline alone (controls). Mice were also immunized with recombinant RgpA after being orally infected with P. gingivalis. After 6 wk, serum was examined for anti-P. gingivalis IgG1 and IgG2a titers and for alveolar bone resorption. RESULTS: Immunization with native RgpA shifted the immune response toward an anti-inflammatory response as demonstrated by decreased proinflammatory cytokine IL-1ß production and greater anti-inflammatory cytokine IL-4 in chamber exudates. Systemically, immunization with recombinant RgpA peptide prevented alveolar bone loss by 50%, similar to immunization with heat-killed whole bacteria. Furthermore, recombinant RgpA shifted the humoral response toward high IgG1 and low IgG2a titers, representing an in vivo anti-inflammatory response. CONCLUSIONS: The present study demonstrates the potential of RgpA to shift the early local immune response toward an anti-inflammatory response while vaccination with recRgpA protected against P. gingivalis-induced periodontitis.
Assuntos
Adesinas Bacterianas/imunologia , Perda do Osso Alveolar/prevenção & controle , Vacinas Bacterianas/uso terapêutico , Infecções por Bacteroidaceae/prevenção & controle , Cisteína Endopeptidases/imunologia , Porphyromonas gingivalis , Perda do Osso Alveolar/microbiologia , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/imunologia , Infecções por Bacteroidaceae/imunologia , Feminino , Cisteína Endopeptidases Gingipaínas , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Porphyromonas gingivalis/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêuticoRESUMO
Synthetic analogues of the cell-wall lipid monomycoloyl glycerol (MMG) are promising as next-generation vaccine adjuvants. In the present study, the thermotropic phase behavior of an array of synthetic MMG analogues was examined by using simultaneous small- and wide-angle X-ray scattering under excess water conditions. The MMG analogues differed in the alkyl chain lengths and in the stereochemistry of the polar glycerol headgroup or of the lipid tails (native-like versus alternative compounds). All MMG analogues formed poorly hydrated lamellar phases at low temperatures and inverse hexagonal (H2) phases at higher temperatures prior to melting. MMG analogues with a native-like lipid acid configuration self-assembled into noninterdigitated bilayers whereas the analogues displaying an alternative lipid acid configuration formed interdigitated bilayers in a subgel (Lc') state. This is in contrast to previously described interdigitated phases for other lipids, which are usually in a gel (Lß) state. All investigated MMG analogues displayed an abrupt direct temperature-induced phase transition from Lc' to H2. This transition is ultimately driven by the lipid chain melting and the accompanying change in molecular shape. No intermediate structures were found, but the entire array of MMG analogues displayed phase coexistence during the lamellar to H2 transition. The structural data also showed that the headgroups of the MMG analogues adopting the alternative lipid acid configuration were ordered and formed a two-dimensional molecular superlattice, which was conserved regardless of the lipid tail length. To our knowledge, the MMG analogues with an alternative lipid acid configuration represent the first example of a lipid system showing both interdigitation and superlattice formation, and as such could serve as an interesting model system for future studies. The MMG analogues are also relevant from a subunit vaccine perspective because they are well-tolerated and display promising immunopotentiating activity. The structural characterization described here will serve as a prerequisite for the rational design of nanoparticulate adjuvants with specific and tailored structural features.
Assuntos
Parede Celular/química , Bicamadas Lipídicas/química , Monoglicerídeos/química , Mycobacterium/química , Células Artificiais , Vacinas Bacterianas/química , Soluções Tampão , Elétrons , Conformação Molecular , Transição de Fase , Fosfatidilcolinas/química , Espalhamento de Radiação , Estereoisomerismo , Temperatura , Termodinâmica , Difração de Raios XRESUMO
Liposome-encapsulated ciprofloxacin for inhalation (CFI) was investigated as a putative postexposure therapeutic for two strains of Francisella tularensis. The efficacies of oral ciprofloxacin and intranasally instilled CFI could not be distinguished in a mouse model of infection with the F. tularensis live vaccine strain (LVS), where a single dose of either formulation offered full protection against a lethal challenge. However, mouse studies with the more virulent Schu S4 strain of F. tularensis demonstrated that a higher level of protection against a lethal aerosol infection is provided by CFI than by oral ciprofloxacin. In addition, using this infection model, it was possible to discriminate the efficacy of intranasally instilled CFI from that of aerosolized CFI, with aerosolized CFI providing full protection after just a single dose. The improved efficacy of CFI compared to oral ciprofloxacin is likely due to the high sustained concentrations of ciprofloxacin in the lung. In summary, CFI may be a promising therapy, perhaps enabling the prophylactic regimen to be shortened, for use in the event of a deliberate release of F. tularensis. The prophylactic efficacy of CFI against other biological warfare (BW) threat agents also warrants investigation.