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Vaccines
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Advances in Oral Vaccine Development
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Advances in Oral Vaccine Development

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Tropical and other Infectious Diseases".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 12323

Special Issue Editor

Dr. Shaun Pennington

E-Mail Website
Guest Editor
Liverpool School of Tropical Medicine, Liverpool, UK
Interests: human immunity; vaccine development; host–pathogen interaction

Special Issue Information

Dear Colleagues,

Pathogens can enter the body through mucosal surfaces. Oral vaccines can create immune responses that protect these surfaces. Oral vaccines are ideal for mass administration programs because they are inexpensive to produce and easy to administer. Trivalent and bivalent oral polio vaccines successfully eradicated wild poliovirus type 2 in 2015 and type 3 in 2019.  Wild poliovirus type 2 was declared eradicated in September 2015; type 3 was declared eradicated in October 2019. However, vaccines have not stopped the spread of wild poliovirus in all countries except for Afghanistan and Pakistan. These findings emphasize the need to focus on oral vaccination programs. We invite researchers to contribute papers to this Special Issue, “Advances in Oral Vaccine Development”. We welcome all original research articles, reviews, or short communications.

Dr. Shaun Pennington
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oral vaccines
  • vaccine development

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Published Papers (6 papers)

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Research

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17 pages, 3929 KiB  
Article
Formulation Attributes Impact Immune Profile of an Oral and Thermostable COVID-19 Subunit Vaccine
by Elodie Burlet, Nissy Thomas, Shanna Carwell, Brett W. Gershman and Garry L. Morefield
Vaccines 2024, 12(10), 1087; https://doi.org/10.3390/vaccines12101087 - 24 Sep 2024
Viewed by 926
Abstract
While approved vaccines for COVID-19 provide protection against severe disease and death, they have limited efficacy in the prevention of infection and virus transmission. Mucosal immunity is preferred over systemic immunity to provide protection at the point of entry against pathogens such as [...] Read more.
While approved vaccines for COVID-19 provide protection against severe disease and death, they have limited efficacy in the prevention of infection and virus transmission. Mucosal immunity is preferred over systemic immunity to provide protection at the point of entry against pathogens such as SARS-CoV-2. VaxForm has developed an oral vaccine delivery platform that elicits mucosal and systemic immune responses by targeting immune cells in the gut through C-type lectin receptors. The technology consists of microencapsulating the vaccine with an enteric polymer, which also results in enhanced thermostability. This article describes the formulation development and in vivo testing of a novel protein-based oral COVID-19 vaccine using this technology. Results demonstrate successful induction of immune response in mice and showed that the particle size of the vaccines following administration can impact the ratio of mucosal to systemic response. Immunogenicity and thermostability of liquid suspension and dry powder versions of the vaccine were compared in mice. The liquid suspension vaccine showed excellent heat resistance by maintaining immunogenicity after 14 days of storage at 60 °C. While further investigation is needed to determine correlates of protection and duration of response for mucosal immunity, this study demonstrates the vaccine’s potential as a COVID-19 booster to enhance mucosal protection in humans and improve global access by lowering the cost of production, removing cold-chain requirements, and allowing self-administration. Full article
(This article belongs to the Special Issue Advances in Oral Vaccine Development)
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21 pages, 3027 KiB  
Article
The JMU-SalVac-System: A Novel, Versatile Approach to Oral Live Vaccine Development
by Andreas Iwanowitsch, Joachim Diessner, Birgit Bergmann and Thomas Rudel
Vaccines 2024, 12(6), 687; https://doi.org/10.3390/vaccines12060687 - 20 Jun 2024
Viewed by 1210
Abstract
Salmonella enterica Serovar Typhi Ty21a (Ty21a) is the only licensed oral vaccine against typhoid fever. Due to its excellent safety profile, it has been used as a promising vector strain for the expression of heterologous antigens for mucosal immunization. As the efficacy of [...] Read more.
Salmonella enterica Serovar Typhi Ty21a (Ty21a) is the only licensed oral vaccine against typhoid fever. Due to its excellent safety profile, it has been used as a promising vector strain for the expression of heterologous antigens for mucosal immunization. As the efficacy of any bacterial live vector vaccine correlates with its ability to express and present sufficient antigen, the genes for antigen expression are traditionally located on plasmids with antibiotic resistance genes for stabilization. However, for use in humans, antibiotic selection of plasmids is not applicable, leading to segregational loss of the antigen-producing plasmid. Therefore, we developed an oral Ty21a-based vaccine platform technology, the JMU-SalVac-system (Julius-Maximilians-Universität Würzburg) in which the antigen delivery plasmids (pSalVac-plasmid-series) are stabilized by a ΔtyrS/tyrS+-based balanced-lethal system (BLS). The system is made up of the chromosomal knockout of the essential tyrosyl-tRNA-synthetase gene (tyrS) and the in trans complementation of tyrS on the pSalVac-plasmid. Further novel functional features of the pSalVac-plasmids are the presence of two different expression cassettes for the expression of protein antigens. In this study, we present the construction of vaccine strains with BLS plasmids for antigen expression. The expression of cytosolic and secreted mRFP and cholera toxin subunit B (CTB) proteins as model antigens is used to demonstrate the versatility of the approach. As proof of concept, we show the induction of previously described in vivo inducible promoters cloned into pSalVac-plasmids during infection of primary macrophages and demonstrate the expression of model vaccine antigens in these relevant human target cells. Therefore, antigen delivery strains developed with the JMU-SalVac technology are promising, safe and stable vaccine strains to be used against mucosal infections in humans. Full article
(This article belongs to the Special Issue Advances in Oral Vaccine Development)
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19 pages, 2897 KiB  
Article
Mucosal Immunization with Spore-Based Vaccines against Mannheimia haemolytica Enhances Antigen-Specific Immunity
by Muhammed Salah Uddin, Angelo Kaldis, Rima Menassa, José Ortiz Guluarte, Daniel R. Barreda, Le Luo Guan and Trevor W. Alexander
Vaccines 2024, 12(4), 375; https://doi.org/10.3390/vaccines12040375 - 1 Apr 2024
Viewed by 2389
Abstract
Background: Mannheimia haemolytica is a bovine respiratory pathogen commonly associated with bacterial bronchopneumonia. Current vaccine strategies have shown variable efficacy in feedlot cattle, and therefore novel vaccines are needed. Bacillus subtilis spores have been investigated as a mucosal vaccine platform, due to their [...] Read more.
Background: Mannheimia haemolytica is a bovine respiratory pathogen commonly associated with bacterial bronchopneumonia. Current vaccine strategies have shown variable efficacy in feedlot cattle, and therefore novel vaccines are needed. Bacillus subtilis spores have been investigated as a mucosal vaccine platform, due to their ability to bind and present antigens to the mucosa and act as an adjuvant. The aim of this study was to develop two spore-based mucosal vaccines targeting M. haemolytica and evaluate their immunogenicity in mice. Methods: Two antigen constructs composed of cholera toxin B subunit, M. haemolytica leukotoxin, and either the M. haemolytica outer membrane protein PlpE (MhCP1) or GS60 (MhCP2) were synthesized, purified and then bound to spores as vaccines. In two separate mice trials, the spore-bound vaccines (Spore-MhCP1 and Spore-MhCP2) were administered to mice through intranasal and intragastric routes, while free antigens were administered intranasally and intramuscularly. Unbound spores were also evaluated intranasally. Antigen-specific serum IgG and mucosal IgA from bronchoalveolar lavage, feces, and saliva were measured after vaccination. Mice sera from all treatment groups were assessed for their bactericidal activity against M. haemolytica. Results: In both mice experiments, intramuscular immunization induced the strongest serum IgG antibody response. However, the intranasal administration of Spore-MhCP1 and Spore-MhCP2 elicited the greatest secretory IgA-specific response against leukotoxin, PlpE, and GS60 in bronchoalveolar lavage, saliva, and feces (p < 0.05). Compared to the intranasal administration of free antigen, spore-bound antigen groups showed greater bactericidal activity against M. haemolytica (p < 0.05). Conclusions: Since intranasally delivered Spore-MhCP1 and Spore-MhCP2 elicited both systemic and mucosal immune responses in mice, these vaccines may have potential to mitigate lung infection in cattle by restricting M. haemolytica colonization and proliferation in the respiratory tract. The efficacy of these mucosal spore-based vaccines merits further assessment against M. haemolytica in cattle. Full article
(This article belongs to the Special Issue Advances in Oral Vaccine Development)
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18 pages, 4048 KiB  
Article
Live-Attenuated Salmonella-Based Oral Vaccine Candidates Expressing PCV2d Cap and Rep by Novel Expression Plasmids as a Vaccination Strategy for Mucosal and Systemic Immune Responses against PCV2d
by Khristine Kaith Sison Lloren and John Hwa Lee
Vaccines 2023, 11(12), 1777; https://doi.org/10.3390/vaccines11121777 - 28 Nov 2023
Cited by 1 | Viewed by 1762
Abstract
Oral vaccines are highly envisaged for veterinary applications due to their convenience and ability to induce protective mucosal immunity as the first line of defense. The present investigation harnessed live-attenuated Salmonella Typhimurium to orally deliver novel expression vector systems containing the Cap and [...] Read more.
Oral vaccines are highly envisaged for veterinary applications due to their convenience and ability to induce protective mucosal immunity as the first line of defense. The present investigation harnessed live-attenuated Salmonella Typhimurium to orally deliver novel expression vector systems containing the Cap and Rep genes from porcine circovirus type 2 (PCV2), a significant swine pathogen. The antigen expression by the vaccine candidates JOL2885 and JOL2886, comprising eukaryotic pJHL204 and pro-eukaryotic expression pJHL270 plasmids, respectively, was confirmed by Western blot and IFA. We evaluated their immunogenicity and protective efficacy through oral vaccination in a mouse model. This approach elicited both mucosal and systemic immunity against PCV2d. Oral administration of the candidates induced PCV2-specific sIgA, serum IgG antibodies, and neutralizing antibodies, resulting in reduced viral loads in the livers and lungs of PCV2d-challenged mice. T-lymphocyte proliferation and flow-cytometry assays confirmed enhanced cellular immune responses after oral inoculation. The synchronized elicitation of both Th1 and Th2 responses was also confirmed by enhanced expression of TNF-α, IFN-γ, IL-4, MHC-I, and MHC-II. Our findings highlight the effectiveness and safety of the constructs with an engineered-attenuated S. Typhimurium, suggesting its potential application as an oral PCV2 vaccine candidate. Full article
(This article belongs to the Special Issue Advances in Oral Vaccine Development)
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16 pages, 1815 KiB  
Article
Lactobacillus acidophilus Expressing Murine Rotavirus VP8 and Mucosal Adjuvants Induce Virus-Specific Immune Responses
by Darby Gilfillan, Allison C. Vilander, Meichen Pan, Yong Jun Goh, Sarah O’Flaherty, Ningguo Feng, Bridget E. Fox, Callie Lang, Harry B. Greenberg, Zaid Abdo, Rodolphe Barrangou and Gregg A. Dean
Vaccines 2023, 11(12), 1774; https://doi.org/10.3390/vaccines11121774 - 28 Nov 2023
Cited by 2 | Viewed by 2152
Abstract
Rotavirus diarrhea-associated illness remains a major cause of global death in children under five, attributable in part to discrepancies in vaccine performance between high- and low-middle-income countries. Next-generation probiotic vaccines could help bridge this efficacy gap. We developed a novel recombinant Lactobacillus acidophilus [...] Read more.
Rotavirus diarrhea-associated illness remains a major cause of global death in children under five, attributable in part to discrepancies in vaccine performance between high- and low-middle-income countries. Next-generation probiotic vaccines could help bridge this efficacy gap. We developed a novel recombinant Lactobacillus acidophilus (rLA) vaccine expressing rotavirus antigens of the VP8* domain from the rotavirus EDIM VP4 capsid protein along with the adjuvants FimH and FliC. The upp-based counterselective gene-replacement system was used to chromosomally integrate FimH, VP8Pep (10 amino acid epitope), and VP8-1 (206 amino acid protein) into the L. acidophilus genome, with FliC expressed from a plasmid. VP8 antigen and adjuvant expression were confirmed by flow cytometry and Western blot. Rotavirus naïve adult BALB/cJ mice were orally immunized followed by murine rotavirus strain ECWT viral challenge. Antirotavirus serum IgG and antigen-specific antibody-secreting cell responses were detected in rLA-vaccinated mice. A day after the oral rotavirus challenge, fecal antigen shedding was significantly decreased in the rLA group. These results indicate that novel rLA constructs expressing VP8 can be successfully constructed and used to generate modest homotypic protection from rotavirus challenge in an adult murine model, indicating the potential for a probiotic next-generation vaccine construct against human rotavirus. Full article
(This article belongs to the Special Issue Advances in Oral Vaccine Development)
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Review

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14 pages, 1135 KiB  
Review
Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery
by Chiara Gai, Margherita Alba Carlotta Pomatto, Maria Chiara Deregibus, Marco Dieci, Alessandro Piga and Giovanni Camussi
Vaccines 2024, 12(2), 200; https://doi.org/10.3390/vaccines12020200 - 15 Feb 2024
Cited by 5 | Viewed by 2910
Abstract
Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNAs, which once incorporated in EVs are protected from enzymatic [...] Read more.
Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNAs, which once incorporated in EVs are protected from enzymatic degradation. This observation has prompted researchers to investigate whether EVs from different sources, including plants, could be used for vaccine delivery. Several studies using human or bacterial EVs expressing mRNA or recombinant SARS-CoV-2 proteins showed induction of a humoral and cell mediated immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have demonstrated advantages in conferring long-lasting immunization and lower toxicity than synthetic nanoparticles. Edible plant-derived EVs were shown to be an alternative to human EVs for vaccine delivery, especially via oral administration. EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation, were stable at room temperature for one year, and were able to trigger a SARS-CoV-2 immune response in mice. Lyophilized oEVs containing the S1 mRNA administered to rats via gavage induced a specific humoral immune response with generation of blocking antibodies, including IgA and Th1 lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and ability to stimulate a humoral and cellular immune response. Full article
(This article belongs to the Special Issue Advances in Oral Vaccine Development)
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