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.

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.

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.

Role of nutrition, infection, and the microbiota in the efficacy of oral vaccines

2018 ◽  
Vol 132 (11) ◽  
pp. 1169-1177 ◽  
Author(s):  
Amrita Bhattacharjee ◽  
Timothy W. Hand
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Oral Vaccines ◽  
Oral Vaccination ◽  
Poor Countries ◽  
Cell Responses ◽  
Mucosal Surfaces ◽  
Resource Poor ◽  
Geographical Locations

Oral vaccines (OVs), provide protection against pathogens that infect mucosal surfaces and their potency relies on their capacity to elicit T- and B-cell responses directed to these surfaces. Oral vaccination efficacy has been found to vary considerably with differences in geographical locations and socioeconomic status. Specifically, in children living in resource-poor countries, undernourishment and chronic gastrointestinal (GI) infection are associated with the failure of OVs, which is a tragic outcome for the children who would benefit most from mucosal-based protection from infection. Both undernutrition and GI infection have been shown to profoundly affect the microbiota, inducing ‘dysbiosis’ characterized by narrowed bacterial diversity and increased frequency of bacterial clades associated with the induction of inflammation. Recent studies have demonstrated that the microbiota exerts a profound effect on the development of mucosal immune responses. Therefore, it seems likely that OV failure in resource-poor regions is affected by alterations to the immune response driven by dysbiotic changes to the microbiota. Here, we review the contribution of the microbiota to OV efficacy in the context of diet and GI infection.

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.

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.

Bilosomes: the answer to oral vaccine delivery?

2001 ◽  
Vol 6 (20) ◽  
pp. 1031-1032 ◽  
Author(s):  
Kathryn Senior
Keyword(s):  
Oral Vaccine ◽  
Vaccine Delivery

scholarly journals Development of a Transgenic Flammulina velutipes Oral Vaccine for Hepatitis B

2019 ◽  
Vol 57 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Li-Hsin Huang ◽  
Hao-Yeh Lin ◽  
Ying-Tzu Lyu ◽  
Chiau-Ling Gung ◽  
Ching-Tsan Huang
Keyword(s):  
Hepatitis B ◽  
Oral Vaccine ◽  
Expression Level ◽  
Flammulina Velutipes ◽  
Total Soluble Protein ◽  
Control Group ◽  
Fruiting Bodies ◽  
Oral Vaccines ◽  
Virus Surface ◽  
Low Expression

Orally administered fungal vaccines show promise for the prevention of infectious diseases. Edible mushrooms are deemed appropriate hosts to produce oral vaccines due to their low production cost and low risk of gene contamination. However, their low expression level of antigens has limited the potential development of oral vaccines using mushrooms. The low expression level might result from impurity of the transgenic mycelia since dikaryotic mycelia are commonly used as transformation materials. In this study, stable transgenic hepatitis B virus surface antigen (HBsAg) in Flammulina velutipes transformants was obtained by Agrobacterium-mediated transformation, followed by fruiting and basidiospore mating. The formation of HBsAg was detected by western blot analysis. The expression levels of HBsAg in transgenic F. velutipes fruiting bodies were (129.3±15.1), (110.9±1.7) and (161.1±8.5) ng/g total soluble protein. However, the values may be underestimated due to incomplete protein extraction. Two of the four pigs in the experimental group produced positive anti-HBsAg-specific IgG after being fed the HBsAg transgenic F. velutipes fruiting bodies for 20 weeks, while no anti-HBsAg antibody was detected in the control group. One of the positive pigs had HBsAg titres of 5.36 and 14.9 mIU/mL in weeks 10 and 14, respectively, but expression faded thereafter. The other positive pig displayed HBsAg titres of 9.75, 17.86 and 39.87 mIU/mL in weeks 14, 18 and 20, respectively. The successful immunogenicity in pigs fed transgenic F. velutipes fruiting bodies demonstrated the potential of using the fungus as an oral vaccine.

M-cell Targeting Acid-resistant Oral Vaccine Delivery for Immunization Against Hepatitis B Infection Using Cationic Solid Lipid Nanoparticles

2021 ◽  
Author(s):  
Surendra Saraf ◽  
Rudra Narayan Sahoo ◽  
Shailesh Jain ◽  
Subrata Mallick
Keyword(s):  
Hepatitis B ◽  
Solid Lipid Nanoparticles ◽  
Oral Vaccine ◽  
Vaccine Delivery ◽  
Lipid Nanoparticles ◽  
Hepatitis B Infection ◽  
Cell Targeting ◽  
M Cell ◽  
Promising Alternative ◽  
Solid Lipid

Abstract Background: Viral infection caused by Hepatitis B is transmitted by permucosal or parenteral exposure and also one of the prime causes of hepatocellular carcinoma and liver cirrhosis. Objectives: M-cell targeting acid-resistant oral vaccine delivery have been formulated for immunization against Hepatitis B infection. Methods: Cationic solid lipid nanoparticles (cSLNs) were prepared utilizing solvent injection technique. Hepatitis B surface antigen (HBsAg) loaded alginate coated cSLNs were anchored with lipopolysaccharide (LPS). SDS-PAGE was performed to evaluate acid degradation protection of prepared formulation. Induction of immunity produced by prepared nanoparticle for Hepatitis B was determined on female Balb/c mice followed by ELISA assays for assessing anti-HBsAg IgG/IgA antibodies in mucosal fluids. Results: Sustained release of HBsAg (60.66 %) has been exhibited from alginate coated cSLNs in comparison to cSLNs without alginate coating (97.72 %) after 48 h. The production of anti-HBs titer in intestinal, salivary and vaginal secretions was 3.41 IU/ml, 3.1 IU/ml and 2.51 IU/ml respectively in comparison to the control group. Integrity of the M-cells has been maintained after binding with SLN, and oral administration delivered the antigen to the desired site of gut. Conclusion: It was found effective in producing antibodies in mucosal immunization against Hepatitis B virus. So, this formulation could be used as a promising alternative preexisting vaccine to prevent Hepatitis B infection.

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