Antigen Delivery to Mucosa-Associated Lymphoid Tissues Using Liposomes as a Carrier

2002 ◽  
Vol 22 (2) ◽  
pp. 355-369 ◽  
Author(s):  
Fan Zhou ◽  
Marian R. Neutra
Keyword(s):  
Oral Vaccine ◽  
Lymphoid Tissues ◽  
M Cells ◽  
Antigen Delivery ◽  
Mucosal Immunization ◽  
Oral Vaccines ◽  
Oral Vaccination ◽  
Particulate Form ◽  
Delivery Vehicles ◽  
Antigen Carrier

Oral vaccination requires an antigen delivery vehicle to protect the antigen and to enhance translocation of the antigen to the mucosa-associated lymphoid tissue. A variety of antigen delivery vehicles including liposomes have been studied for mucosal immunization. The advantages of liposome formulations are their particulate form and the ability to accommodate immunomodulators and targeting molecules in the same package. Many conventional liposomes are variably unstable in acids, pancreatic juice and bile. Nevertheless, carefully designed liposomes have demonstrated an impressive efficacy in inducing mucosal IgA responses, compared to free antigens and other delivery vehicles. However, liposomes as an oral vaccine vehicle are not yet optimized. To design liposomes that are stable in the harsh intestinal environment and are efficiently taken up by the M cells remains a challenge. This review summarizes recent research efforts using liposomes as an antigen carrier for oral vaccines with practical attention to liposome designs and interaction with the M cells.

scholarly journals Oral Immunization with Recombinant Lactobacillus plantarum Induces a Protective Immune Response in Mice with Lyme Disease

2008 ◽  
Vol 15 (9) ◽  
pp. 1429-1435 ◽  
Author(s):  
Beatriz del Rio ◽  
Raymond J. Dattwyler ◽  
Miguel Aroso ◽  
Vera Neves ◽  
Luciana Meirelles ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Lactobacillus Plantarum ◽  
Oral Vaccine ◽  
Oral Immunization ◽  
Microbial Pathogens ◽  
Antigen Delivery ◽  
Mucosal Immunization ◽  
Mucosal Delivery ◽  
Vaccine Antigens ◽  
Delivery Vehicles

ABSTRACT Mucosal immunization is advantageous over other routes of antigen delivery because it can induce both mucosal and systemic immune responses. Our goal was to develop a mucosal delivery vehicle based on bacteria generally regarded as safe, such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as a proof of concept. We demonstrate that an oral vaccine based on live recombinant Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi infection. Our method of expressing vaccine antigens in L. plantarum induces both systemic and mucosal immunity after oral administration. This platform technology can be applied to design oral vaccine delivery vehicles against several microbial pathogens.

scholarly journals Oral Biologic Delivery: Advances Toward Oral Subunit, DNA, and mRNA Vaccines and the Potential for Mass Vaccination During Pandemics

2021 ◽  
Vol 61 (1) ◽  
pp. 517-540 ◽  
Author(s):  
Jacob William Coffey ◽  
Gaurav Das Gaiha ◽  
Giovanni Traverso
Keyword(s):  
Oral Cavity ◽  
Oral Vaccine ◽  
Vaccine Delivery ◽  
Mass Vaccination ◽  
Oral Vaccines ◽  
Gi Tract ◽  
Oral Vaccination ◽  
Enteric Diseases ◽  
Mucosal Surfaces ◽  
Inactivated Vaccines

Oral vaccination enables pain-free and self-administrable vaccine delivery for rapid mass vaccination during pandemic outbreaks. Furthermore, it elicits systemic and mucosal immune responses. This protects against infection at mucosal surfaces, which may further enhance protection and minimize the spread of disease. The gastrointestinal (GI) tract presents a number of prospective mucosal inductive sites for vaccine targeting, including the oral cavity, stomach, and small intestine. However, currently available oral vaccines are effectively limited to live-attenuated and inactivated vaccines against enteric diseases. The GI tract poses a number of challenges,including degradative processes that digest biologics and mucosal barriers that limit their absorption. This review summarizes the approaches currently under development and future opportunities for oral vaccine delivery to established (intestinal) and relatively new (oral cavity, stomach) mucosal targets. Special consideration is given to recent advances in oral biologic delivery that offer promise as future platforms for the administration of oral vaccines.

Peptide nanofiber–CaCO3 composite microparticles as adjuvant-free oral vaccine delivery vehicles

2016 ◽  
Vol 4 (9) ◽  
pp. 1640-1649 ◽  
Author(s):  
Joshua D. Snook ◽  
Charles B. Chesson ◽  
Alex G. Peniche ◽  
Sara M. Dann ◽  
Adriana Paulucci ◽  
...  
Keyword(s):  
Mucosal Immunity ◽  
Oral Vaccine ◽  
Vaccine Delivery ◽  
Oral Vaccination ◽  
Delivery Vehicles ◽  
Gi Infections ◽  
Mucosal Pathogens

To combat mucosal pathogens that cause gastrointestinal (GI) infections, local mucosal immunity is required which is best achieved through oral vaccination.

scholarly journals A Single Dose of Oral BCG Moreau Fails to Boost Systemic IFN-γResponses to Tuberculin in Children in the Rural Tropics: Evidence for a Barrier to Mucosal Immunization

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Maritza Vaca ◽  
Ana-Lucia Moncayo ◽  
Catherine A. Cosgrove ◽  
Martha E. Chico ◽  
Luiz R. Castello-Branco ◽  
...  
Keyword(s):  
Rural Communities ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Study Groups ◽  
Mucosal Immunization ◽  
Oral Vaccines ◽  
Oral Vaccination ◽  
Peripheral Blood Mononuclear ◽  
Before And After

Immune responses to oral vaccines are impaired in populations living in conditions of poverty in developing countries, and there is evidence that concurrent geohelminth infections may contribute to this effect. We vaccinated 48 children living in rural communities in Ecuador with a single oral dose of 100 mg of BCG Moreau RDJ and measured the frequencies of tuberculin-stimulated peripheral blood mononuclear cells expressing IFN-γbefore and after vaccination. Vaccinated children had active ascariasis(n=20)or had been infected but received short-(n=13)or long-term(n=15)repeated treatments with albendazole prior to vaccination to treat ascariasis. All children had a BCG scar from neonatal vaccination. There was no evidence of a boosting of postvaccination IFN-γresponses in any of the 3 study groups. Our data provide support for the presence of a barrier to oral vaccination among children from the rural tropics that appeared to be independent of concurrent ascariasis.

Mechanisms of vaccine adjuvanticity at mucosal surfaces

2000 ◽  
Vol 1 (1) ◽  
pp. 3-24 ◽  
Author(s):  
Dennis L. Foss ◽  
Michael P. Murtaugh
Keyword(s):  
Molecular Mechanisms ◽  
Oral Vaccine ◽  
Vaccine Antigen ◽  
Lymphoid Tissues ◽  
Vaccine Adjuvants ◽  
Intestinal Immunity ◽  
Oral Vaccines ◽  
Rational Development ◽  
Mucosal Surfaces ◽  
Gut Mucosa

AbstractThe vast majority of pathogens invade via mucosal surfaces, including those of the intestine. Vaccination directly on these surfaces may induce local protective immunity and prevent infection and disease. Although vaccine delivery to the gut mucosa is fraught with obstacles, immunization can be enhanced using adjuvants with properties specific to intestinal immunity. In this review, we present three general mechanisms of vaccine adjuvant function as originally described by Freund, and we discuss these principles with respect to intestinal adjuvants in general and to the prototypical mucosal adjuvant, cholera toxin. The key property of intestinal adjuvants is to induce an immunogenic context for the presentation of the vaccine antigen. The success of oral vaccine adjuvants is determined by their ability to induce a controlled inflammatory response in the gut-associated lymphoid tissues, characterized by the expression of various costimulatory molecules and cytokines. An understanding of the specific molecular mechanisms of adjuvanticity in the gut will allow the rational development of safe and effective oral vaccines.

scholarly journals Advances in Oral Subunit Vaccine Design

Vaccines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Hans Van der Weken ◽  
Eric Cox ◽  
Bert Devriendt
Keyword(s):  
Immune Responses ◽  
Immune Cell ◽  
Oral Vaccine ◽  
Vaccine Design ◽  
Secretory Iga ◽  
Lymphoid Tissues ◽  
Oral Vaccines ◽  
Subunit Vaccines ◽  
Vaccine Antigens ◽  
Gut Immunity

Many pathogens invade the host at the intestinal surface. To protect against these enteropathogens, the induction of intestinal secretory IgA (SIgA) responses is paramount. While systemic vaccination provides strong systemic immune responses, oral vaccination is the most efficient way to trigger protective SIgA responses. However, the development of oral vaccines, especially oral subunit vaccines, is challenging due to mechanisms inherent to the gut. Oral vaccines need to survive the harsh environment in the gastrointestinal tract, characterized by low pH and intestinal proteases and need to reach the gut-associated lymphoid tissues, which are protected by chemical and physical barriers that prevent efficient uptake. Furthermore, they need to surmount default tolerogenic responses present in the gut, resulting in suppression of immunity or tolerance. Several strategies have been developed to tackle these hurdles, such as delivery systems that protect vaccine antigens from degradation, strong mucosal adjuvants that induce robust immune responses and targeting approaches that aim to selectively deliver vaccine antigens towards specific immune cell populations. In this review, we discuss recent advances in oral vaccine design to enable the induction of robust gut immunity and highlight that the development of next generation oral subunit vaccines will require approaches that combines these solutions.

scholarly journals Protection of Teleost Fish against Infectious Diseases through Oral Administration of Vaccines: Update 2021

2021 ◽  
Vol 22 (20) ◽  
pp. 10932
Author(s):  
Jarl Bøgwald ◽  
Roy A. Dalmo
Keyword(s):  
Oral Administration ◽  
Teleost Fish ◽  
Oral Vaccine ◽  
Infectious Pancreatic Necrosis Virus ◽  
Infectious Salmon Anaemia Virus ◽  
Oral Vaccines ◽  
Oral Vaccination ◽  
Mass Immunization ◽  
Recent Developments ◽  
Pancreatic Necrosis Virus

Immersion and intraperitoneal injection are the two most common methods used for the vaccination of fish. Because both methods require that fish are handled and thereby stressed, oral administration of vaccines as feed supplements is desirable. In addition, in terms of revaccination (boosting) of adult fish held in net pens, oral administration of vaccines is probably the only feasible method to obtain proper protection against diseases over long periods of time. Oral vaccination is considered a suitable method for mass immunization of large and stress-sensitive fish populations. Moreover, oral vaccines may preferably induce mucosal immunity, which is especially important to fish. Experimental oral vaccine formulations include both non-encapsulated and encapsulated antigens, viruses and bacteria. To develop an effective oral vaccine, the desired antigens must be protected against the harsh environments in the stomach and gut so they can remain intact when they reach the lower gut/intestine where they normally are absorbed and transported to immune cells. The most commonly used encapsulation method is the use of alginate microspheres that can effectively deliver vaccines to the intestine without degradation. Other encapsulation methods include chitosan encapsulation, poly D,L-lactide-co-glycolic acid and liposome encapsulation. Only a few commercial oral vaccines are available on the market, including those against infectious pancreatic necrosis virus (IPNV), Spring viremia carp virus (SVCV), infectious salmon anaemia virus (ISAV) and Piscirickettsia salmonis. This review highlights recent developments of oral vaccination in teleost fish.

Phage Display–Derived Ligand for Mucosal Transcytotic Receptor GP-2 Promotes Antigen Delivery to M Cells and Induces Antigen-Specific Immune Response

2017 ◽  
Vol 22 (7) ◽  
pp. 879-886
Author(s):  
Inam Ullah Khan ◽  
Jiansheng Huang ◽  
Rui Liu ◽  
Jingbo Wang ◽  
Jun Xie ◽  
...  
Keyword(s):  
Immune Response ◽  
Phage Display ◽  
Ex Vivo ◽  
Oral Vaccine ◽  
Green Fluorescence Protein ◽  
Cytokine Secretion ◽  
Phage Library ◽  
M Cells ◽  
Antigen Delivery

Successful oral immunization depends on efficient delivery of antigens (Ags) to the mucosal immune induction site. Glycoprotein-2 (GP-2) is an integral membrane protein that is expressed specifically on M cells within follicle-associated epithelium (FAE) and serves as transcytotic receptor for luminal Ags. In this study, we selected peptide ligands against recombinant human GP-2 by screening a phage display library and evaluated their interaction with GP-2 in vitro and ex vivo. Selected peptides were conjugated to the C-terminal of enhanced green fluorescence protein (EGFP) and evaluated for their ability to induce an immune response in mice. One of our selected peptides, Gb-1, showed high binding affinity to GP-2 and, when fused to EGFP, significantly increased the uptake of EGFP by M cells compared to EGFP alone. After oral administration, the Gb1-EGFP fusion induced efficient mucosal and systemic immune responses in mice measured at the level of antigen-specific serum and fecal antibodies, cytokine secretion, and lymphocyte proliferation. Furthermore, the IgG subclasses and cytokine secretion showed that ligand Gb-1 induced a Th2-type immune response. Collectively, our findings suggest that the ligand we selected through phage library screening is capable of targeting Ags to GP-2 on M cells and can be used as an oral vaccine adjuvant.

scholarly journals Oral Vaccination of Grass Carp (Ctenopharyngodon idella) with Baculovirus-Expressed Grass Carp Reovirus (GCRV) Proteins Induces Protective Immunity against GCRV Infection

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 41
Author(s):  
Changyong Mu ◽  
Qiwang Zhong ◽  
Yan Meng ◽  
Yong Zhou ◽  
Nan Jiang ◽  
...  
Keyword(s):  
Survival Rate ◽  
Grass Carp ◽  
Oral Vaccine ◽  
Serum Antibody ◽  
Ctenopharyngodon Idella ◽  
Control Group ◽  
Oral Vaccination ◽  
Grass Carp Reovirus ◽  
Silkworm Pupae ◽  
Grass Carp Ctenopharyngodon Idella

The grass carp reovirus (GCRV) causes severe hemorrhagic disease with high mortality and leads to serious economic losses in the grass carp (Ctenopharyngodon idella) industry in China. Oral vaccine has been proven to be an effective method to provide protection against fish viruses. In this study, a recombinant baculovirus BmNPV-VP35-VP4 was generated to express VP35 and VP4 proteins from GCRV type Ⅱ via Bac-to-Bac baculovirus expression system. The expression of recombinant VP35-VP4 protein (rVP35-VP4) in Bombyx mori embryo cells (BmE) and silkworm pupae was confirmed by Western blotting and immunofluorescence assay (IFA) after infection with BmNPV-VP35-VP4. To vaccinate the grass carp by oral route, the silkworm pupae expressing the rVP35-VP4 proteins were converted into a powder after freeze-drying, added to artificial feed at 5% and fed to grass carp (18 ± 1.5 g) for six weeks, and the immune response and protective efficacy in grass carp after oral vaccination trial was thoroughly investigated. This included blood cell counting and classification, serum antibody titer detection, immune-related gene expression and the relative percent survival rate in immunized grass carp. The results of blood cell counts show that the number of white blood cells in the peripheral blood of immunized grass carp increased significantly from 14 to 28 days post-immunization (dpi). The differential leukocyte count of neutrophils and monocytes were significantly higher than those in the control group at 14 dpi. Additionally, the number of lymphocytes increased significantly and reached a peak at 28 dpi. The serum antibody levels were significantly increased at Day 14 and continued until 42 days post-vaccination. The mRNA expression levels of immune-related genes (IFN-1, TLR22, IL-1β, MHC I, Mx and IgM) were significantly upregulated in liver, spleen, kidney and hindgut after immunization. Four weeks post-immunization, fish were challenged with virulent GCRV by intraperitoneal injection. The results of this challenge study show that orally immunized group exhibited a survival rate of 60% and relative percent survival (RPS) of 56%, whereas the control group had a survival rate of 13% and RPS of 4%. Taken together, our results demonstrate that the silkworm pupae powder containing baculovirus-expressed VP35-VP4 proteins could induce both non-specific and specific immune responses and protect grass carp against GCRV infection, suggesting it could be used as an oral vaccine.

Rabbit M cells and dome enterocytes are distinct cell lineages

2001 ◽  
Vol 114 (11) ◽  
pp. 2077-2083
Author(s):  
Hugues Lelouard ◽  
Alain Sahuquet ◽  
Hubert Reggio ◽  
Philippe Montcourrier
Keyword(s):  
Lymphoid Tissues ◽  
M Cells ◽  
Relative Distribution ◽  
M Cell ◽  
Epithelial Surface ◽  
Cell Lineages ◽  
Proliferative Zone ◽  
Early Appearance ◽  
Distinct Cell ◽  
Constant Distribution

We have studied the M cell origin and differentiation pathway in rabbit gut-associated lymphoid tissues. Micro-dissected domes and epithelium isolated by ethylene diamine tetra acetic acid detachment allowed us to view the whole epithelial surface from the bottom of crypts to the top of domes. We used monoclonal antibodies specific to the apex of either M cells or dome enterocytes, lectins, and antibodies to vimentin in appendix, distal Peyer’s patches and caecal patches. The earliest vimentin-labeled M cells were observed in the BrdU-positive proliferative zone of dome-associated crypts. Gradual differentiation of the M cell vimentin cytoskeleton started at this site to progressively give rise to the first pocket-forming M cells in the upper dome. Therefore, these mitotic cells of the crypts appear as the direct precursors of M cells. In addition to an early appearance of M cell markers, a regular mosaic-like relative distribution of M cells and dome enterocytes was already detected in the vicinity of crypts, similar to that observed on the lateral surface of domes where functional M cells lie. This constant distribution implies that there is no trans-differentiation of enterocytes to M cells along the crypt-dome axis. Together, these observations provide very strong evidence in favor of an early commitment in crypts of M cell and enterocyte distinct lineages.

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