Edible Vaccines Research Articles

Edible vaccines from fruit and vegetables: A comprehensive review

Edible vaccines from fruit and vegetables: A comprehensive review

Duckweeds as edible vaccines in the animal farming industry.

Animal diseases are among the most debilitating issues in the animal farming industry, resulting in decreased productivity and product quality worldwide. An emerging alternative to conventional injectable vaccines is edible vaccines, which promise increased delivery efficiency while maintaining vaccine effectiveness. One of the most promising platforms for edible vaccines is duckweeds, due to their high growth rate, ease of transformation, and excellent nutritional content. This review explores the potential, feasibility, and advantages of using duckweeds as platforms for edible vaccines. Duckweeds have proven to be superb feed sources, as evidenced by numerous improvements in both quantity (e.g., weight gain) and quality (e.g., yolk pigmentation). In terms of heterologous protein production, duckweeds, being plants, are capable of expressing proteins with complex structures and post-translational modifications. Research efforts have focused on the development of duckweed-based edible vaccines, including those against avian influenza, tuberculosis, Newcastle disease, and mastitis, among others. As with any emerging technology, the development of duckweeds as a platform for edible vaccines is still in its early stages compared to well-established injectable vaccines. It is evident that more proof-of-concept studies are required to bring edible vaccines closer to the current standards of conventional vaccines. Specifically, the duckweed expression system needs further development in areas such as yield and growth rate, especially when compared to bacterial and mammalian expression systems. Continued efforts in this field could lead to breakthroughs that significantly improve the resilience of the animal farming industry against disease threats.

Investigation of the toxicity and safety concerns of transgenic maize seeds expressing immunogenic F and HN protein genes against Newcastle disease virus.

The presented study investigated the potential toxicity and safety concerns associated with transgenic maize seeds expressing immunogenic F and HN protein genes against Newcastle disease virus (NDV). The experiment involved feeding Sprague-Dawley rats with transgenic maize seeds formulated into standard diets at levels of 30% (w/w) for a duration of 90days. The rats were divided into three groups, with 10 rats per group. We assessed various parameters including overall appearance, feed consumption, body weight, organ weight, hematological parameters, serum chemistry, and histopathology. The results of these assessments were compared between the control group and the treatment groups. The study findings revealed that there were no significant differences between the control and treatment groups in terms of overall appearance, feed consumption, body weight, organ weight, hematological parameters, serum chemistry, microscopic histopathology, and gross appearance of tissues. These observations suggest that the consumption of transgenic maize seeds did not lead to any treatment-related adverse effects or toxicological issues. Furthermore, the transgenic maize seeds were found to be nutritionally equivalent to their non-transgenic counterpart. Overall, no physiological, pathological, or molecular toxicity was observed in the Rats fed with transgenic feed.However, it is important to note that this study focused specifically on the parameters measured and the outcomes observed in Sprague-Dawley rats, and further research and studies are necessary to fully evaluate the safety and potential applications of transgenic edible vaccines in humans or other animals.

Leveraging the potential of bacterial lateral gene transfer in boosting the efficacy of an edible probiotic prototype yogurt vaccine for COVID-19

Administration of coronavirus disease-2019 (COVID-19) vaccines with appropriate booster doses through painful injections under clinical supervision was challenging during the recent COVID-19 pandemic. As an alternative solution, we designed a safer, edible probiotic yogurt vaccine prototype (YoVac) that can be orally consumed by circumventing painful injections and clinical supervision. We hypothesized that YoVac prepared using Lactobacillus carrying an antigen coding gene (donor) can transfer the same to other bacteria (recipients) in the human gut microbiome (hgMb) through lateral gene transfer (LGT) for boosted antigen levels potentially triggering a robust immune response. In this study we confirmed the in vitro LGT efficiency of a plasmid (pRBD-Ampr) containing severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) spike protein-receptor binding domain (RBD) coding gene along with an ampicillin-resistance gene (selection marker) from the probiotic Lactobacillus (donor) cultured from homemade yogurt to E. coli and Helicobacter pylori (recipients). Both the donor and recipient bacteria not only exhibited ampicillin-resistance from pRBD-Ampr but also expressed RBD protein. Furthermore, Lactobacillus isolated from YoVac consistently showed the expression of RBD protein over a period of one month confirming the shelf life of our prototype stored at 4 °C. Taken together, our in vitro results provide a preliminary basis for the potential in vivo transfer of RBD coding gene from YoVac to other bacterial species in the hgMb through LGT and may potentially boost the vaccine dosage by delegating them.

Agrobacterium tumefaciens: Biology and application in genetic engineering

Agrobacterium tumefaciens is a rod-shaped soil bacterium renowned for its unique ability to transfer tumour-inducing plasmid (Ti plasmid) segments to plant cells. This mechanism has been extensively exploited in plant genetic engineering. This review delves into the intricate biological interactions between A. tumefaciens and plant cells, including the critical steps of bacterial attachment, activation of virulence (Vir) genes, generation and transport of the T-complex, and integration of T-DNA into the plant chromosome. Furthermore, the review examines the engineering of A. tumefaciens as a transformation tool, focusing on the modifications of Ti plasmids to create binary and co-integrative vector systems, which have significantly improved the efficiency and versatility of transformation protocols. The paper also highlights applications of Agrobacterium-mediated transformation in the production of edible vaccines. By providing a detailed examination of the biological, technical, and practical aspects of Agrobacterium-mediated transformation, this review aims to offer insights into optimizing this technique for various plant biotechnology applications. Ultimately, understanding and improving Agrobacterium-mediated transformation is crucial for advancing plant biotechnology.

Novel edible multi-epitope vaccine construct against Enterococcus faecalis

Novel edible multi-epitope vaccine construct against Enterococcus faecalis

Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection

BackgroundHelicobacter pylori (H. pylori) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) can, however, reduce the effectiveness of oral vaccinations. For the creation of an edible vaccine, L. lactis has been proposed as a means of delivering vaccine antigens.ResultsWe developed a plSAM (pNZ8148-SAM) that expresses a multiepitope vaccine antigen SAM-WAE containing Urease, HpaA, HSP60, and NAP extracellularly (named LL-plSAM-WAE) to increase the efficacy of oral vaccinations. We then investigated the immunogenicity of LL-plSAM-WAE in Balb/c mice. Mice that received LL-plSAM-WAE or SAM-WAE with adjuvant showed increased levels of antibodies against H. pylori, including IgG and sIgA, and resulted in significant reductions in H. pylori colonization. Furthermore, we show that SAM-WAE and LL-plSAM-WAE improved the capacity to target the vaccine to M cells.ConclusionsThese findings suggest that recombinant L. lactis could be a promising oral mucosa vaccination for preventing H. pylori infection.

A Tasty Twist: Exploring the Potential of Edible Vaccines

A biological preparation known as a vaccine offers active acquired immunity to a specific infectious or malignant disease. There are various vaccine varieties, such as: inactivated vaccines. live-attenuated immunizations. mRNA (messenger RNA) vaccines. vaccinations include subunits, recombinants, polysaccharides, and conjugates. Genetically engineered crops with antigens for particular diseases are known as edible vaccines. Due to the vaccine's simplicity of culture, this lowers the product cost. Since they don't require adjuvants that strengthen the susceptible response, edible vaccines are a viable method of immunization delivery. In terms of vacuity, storage, medication, product, and transportation, edible vaccines are also economical. Foods under such operation include potato, banana, lettuce, soybean, rice, lettuce, apple, peas, soyabean, cherry tomatoes, alfalfa, tomatoes, carrot etc. This review focuses on the development of edible vaccines over the years and the various lookouts it holds as technology keeps developing. The evolution of vaccines has led to the discovery of new forms of vaccination that are efficacious and cover a broad array of disease.

Seed-specific expression of porcine verotoxigenic Escherichia coli antigens in tobacco plants as a potential model of edible vaccines

Vaccines can reduce the use of antibiotics by preventing specific infective diseases in pigs. Plant-based edible vaccines are particularly attractive because, upon oral ingestion via feed, they can elicit the local immune system against a foreign disease-causing organism. The aim of this study was to engineer two different independent lines of tobacco plants for the seed-specific expression of immunogenic proteins of VTEC as a model of an edible vaccine. For each antigen, fifty Nicotiana tabacum L. cv Xanthi leaf disks were transformed by agroinfection for the seed-specific expression of the structural parts of the fimbrial subunit FedF of F18 and the B-subunit of Vt2e genes. The synthetic genes, optimized by the codon adaptation index for their expression in tobacco, were inserted into expression cassettes under the control of β-conglycinin promoter. Regenerated tobacco plants (T0) were characterized by molecular and immunoenzymatic techniques. Our results showed that both FedF and Vt2eB genes were integrated into tobacco genome efficiently (> 80%) and they are also maintained in the second generation (T1). Western blotting analyses carried out on the positive producing lines, showed the tissue-specific expression in seeds and the temporal protein accumulation in the mid-late maturation phases. The enzyme-linked immunosorbent assay showed seed expression levels of 0.09 to 0.29% (from 138 to 444 µg/g of seeds) and 0.21 to 0.43% (from 321 to 658 µg/g of seeds) of total soluble protein for the FedF and Vt2eB antigens, respectively. This study confirmed the seed-specific expression of the selected antigens in plant seeds. The expression level is suitable for seed-based edible vaccination systems, which could represent a cost-effective way to prevent VTEC infection. Our findings encourage further in vivo studies focused on the activation of the local immune response.

Edible Vaccines: A Patent-Driven Exploration of Immunization Technologies.

Vaccines are biological preparations that improve immunity to particular diseases. Particularly for poor developing nations, edible vaccines show significant potential as a financially advantageous, simple to administer, straightforward to store, fail-safe, and socially and culturally acceptable vaccine delivery system. A vaccine incorporates the gene-encoding bacterial or viral disease-causing agent in plants without losing its immunogenic property. Potatoes, tomatoes, rice, soybeans, and bananas are the primary plants for edible vaccines. It activates the systemic and mucosal immunity responses against a foreign disease-causing organism. It offers exciting possibilities to reduce diseases like hepatitis B, rabies, HIV/AIDS (human immunodeficiency virus infection and acquired immune deficiency syndrome), etc. These vaccines provide many benefits, like being convenient to administer, efficiently storing, and readily acceptable drug delivery systems for patients of different age groups. So, an edible vaccine may be the most convenient vaccine to improve immunity. However, there are a lot of technical and regulatory challenges to overcome in the way of edible vaccine technology. Though all seem surmountable, various technical obstacles and regulatory and non-scientific challenges need to be overcome. Moreover, edible vaccine patents represent a cutting-edge area of biotechnology, where the integration of genetic material into edible substances holds great promise for revolutionizing vaccination methods. These patents aim to harness the potential of plants and other edibles to stimulate immune responses, offering a potential alternative to traditional injectable vaccines. This review states the technologies, host plants, current status, recent patents, the future of this new preventive modality, and different regulatory issues concerning edible vaccines.

Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans.

Plant-based edible vaccines that provide two-layered protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outweigh the currently used parenteral types of vaccines, which predominantly cause a systemic immune response. Here, we engineered and selected a transgenic tomato genotype (TOMAVAC) that stably synthesized an antigenic S1 protein of SARS-CoV-2. Two-course spaced force-feeding of mice with ≈5.4 μg/ml TOMAVAC increased up to 16-fold the synthesis of RBD-specific NAbs in blood serum and the significant induction of S-IgA in intestinal lavage fluid. In a surrogate virus neutralization test, TOMAVAC-induced NAbs had 15-25% viral neutralizing activity. The results suggested early evidence of the immunogenicity and protectivity of TOMAVAC against the coronavirus disease 2019 (COVID-19) infection. Furthermore, we observed a positive trend of statistically significant 1.2-fold (average of +42.28 BAU/ml) weekly increase in NAbs in the volunteers' serum relative to the initial day. No severe side effects were observed, preliminarily supporting the safety of TOMAVAC. With the completion of future large-scale studies, higher-generation TOMAVAC should be a cost-effective, ecologically friendly, and widely applicable novel-generation COVID-19 vaccine, providing two-layered protection against SARS-CoV-2.

Progress in vaccines against peste des petits ruminants virus

Peste des petits ruminants (PPR) is a highly contagious and economically important viral disease of both domestic (goats and sheep) and wild small ruminants. Due to the devastating effect of this disease on livestock and livelihoods, the Food and Agriculture Organization of the United Nations (FAO) and the World Organization for Animal Health (WOAH) endorsed the Global Strategy for the Control and Eradication of PPR (PPR GCES) and launched the PPR Global Eradication Programme (PPR GEP) to eradicate PPRV by 2030. In order to achieve this goal, a potent, safe and efficacious live-attenuated PPR vaccine with long-lasting immunity is available for immunoprophylaxis. However, the live-attenuated PPR vaccines are thermolabile and require maintenance of an effective cold chain to deliver to the field. In addition, infected animals cannot be differentiated from vaccinated ones (DIVA). To overcome these limitations, some new generation PPR vaccines have been developed: poxvirus vaccine, positive and negative marker vaccine through reverse genetic approach, chimeric vaccine, anti-idiotypic vaccine, subunit vaccine, virus-like particles vaccine, edible vaccine and combined vaccines. Novel recombinant PPR DIVA vaccines were evaluated in goats for safety and efficacy, and all vaccinated animals were clinically protected against an intranasal PPRV challenge. Furthermore, newly developed ELISAs were capable of differentiating between infected and vaccinated animals. Therefore, these DIVA vaccines and the associated tests can facilitate the serological monitoring process and speed up global PPR eradication through vaccination.

SWOT Analysis of Edible Vaccine for Public Health

SWOT Analysis of Edible Vaccine for Public Health

Recent Progress and Challenges in the Development of Edible Vaccines Produced by Genetically Modified Plants.

Biotechnologists have pioneered the idea of an edible vaccination in recent years. Subunit vaccines, such as those used to create edible vaccines, involve the introduction of certain genes into transgenic plants, which are subsequently coaxed into producing the corresponding protein. Bananas, potatoes, legumes, lettuce, soybeans, corn, and rice are all examples of foods that fall under this category. They have a low unit cost, can be stored conveniently, and are simple to administer to patients of varying ages. There is great hope that the use of edible vaccinations, particularly in underdeveloped countries, could drastically reduce the prevalence of diseases, including measles, cholera, hepatitis B, and diarrhea. The development of effective and widely applicable edible vaccination, however, faces a number of technological and regulatory hurdles. When compared to traditional immunizations, edible vaccines offer significant cost savings, increased productivity, and reduced risk. It raises the possibility of a more efficient approach to illness prevention. This article includes important uses, production, host plants, benefits, drawbacks, mechanism of action, and many regulatory difficulties related to edible vaccines. In this article, we have discussed the most recent developments and successes with edible and intradermal vaccines in terms of the system used for immunogen production, the molecular properties of these vaccines, and their ability to generate a protective systemic and mucosal response.

Development of transgenic algae strain expressing CTB-M2e fusion gene an approach towards the development of a universal edible vaccine in Algae.

Avian Influenza, the most studied virus, is of high concern due to its zoonotic pandemic potential. In recent years, several influenza vaccines have been used with the broad goal of managing and in certain cases, eliminating the disease. The matrix 2 extracellular domain (M2e), is one of the key targets of the universal influenza vaccine, a liner peptide that is conserved throughout all influenza A subtypes virus. Many recombinant influenza proteins have been expressed in yeast and plants for vaccine development. A remarkable development has been made in the field of biotechnology to explore the potential of microalga as an expression host. In this study, we designed a fusion gene code for M2e peptide and CTB protein as M2e's natural form has a low level of immunogenicity. The fusion gene was cloned in the Chloroplast transformation vector pSRSapI and expressed in the TN72 mutant strain of Chlamydomonas reinhardii. The expression of the targeted protein was confirmed by ECL western blot analysis. A GM1-ELISA was carried out to detect the affinity of fusion protein for GM1 monosialoganglioside and the significant P-value is lower than 0.05. Immunogenicity assay on chicken detected the anti-M2e bodies in chicken serum. This study gives evidence of therapeutic protein production through algae chloroplast and a stable, selection free and low cost oral delivery for universal vaccine against influenza A virus.

Modern Plant Biotechnology: An Antidote against Global Food Insecurity

Food insecurity has become a pressing issue on a worldwide scale as the globe plows through a food crisis. The disastrous impact of this menace has been exacerbated by climate change, frequent conflicts, pandemic outbreaks, and the global economic recession, which have been prevalent in recent years. Although food insecurity prevails globally, it is especially critical in some regions in Africa, East and Southeast Asia, and South America. Several efforts have been made to curb food insecurity; however, none have been able to curtail it sufficiently. Genetic engineering of crops is a fast-growing technology that could be a viable tool for mitigating food insecurity. Crop varieties resistant to pests and diseases, abiotic stress, spoilage, or specific herbicides have been developed using this technology. Crops have been modified for increased yield, nutritional content, essential vitamins, and micro-mineral fortification. More intriguing is the advent of plant-derived edible vaccines, which prove equally effective and significantly affordable. However, in many countries, government policies pose a limiting factor for the acceptance of this technology. This article discusses the genetic modification of crops, highlighting its origins, methods, applications, achievements, impact, acceptance, distribution, and potential as a viable antidote to global food insecurity.

Exploring the Potential of Plant-Based CTB-INS Oral Vaccines in Treating Type 1 Diabetes

The 19th century saw the development of vaccines, which were biological preparations designed to enhance immunity against specific diseases. Edible vaccines function by stimulating both systemic and mucosal immune responses against foreign pathogens, and they may potentially protect the host from autoimmunity. The mucosal surfaces provide a convenient and rapid route for delivering therapeutic small molecules. This is due to their large surface areas and easy administration. The effectiveness of mucosal immunization relies on the fact that mucous membranes represent the body’s largest immunogenic organ. Within this interface, there is a well-organized lymphatic structure known as MALT (mucosa-associated lymphoid tissue), which includes both T and B cells and encompasses the adaptive arms of the immune system. Oral vaccines specifically stimulate immune responses in the gut-associated lymphoid tissue (GALT), which consists of lymph nodes, Payer’s patches (where B cells make up about 75% of the population and T cells account for approximately 20%), and isolated lymphoid follicles within the gastrointestinal tract (GIT). However, a significant challenge in developing vaccines is the rapid degradation of antigens within the harsh environment of the digestive tract, which hampers effective protein delivery to the GIT. In light of recent proteomic analysis revealing strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1) in DCs inoculated with the Cholera toxin B-subunit-Insulin fusion protein vaccine (CTB-INS), we are interested in investigating the effects of transgene integration into a selected plant cell as an edible vaccine.

Edible microalgae: potential candidate for developing edible vaccines.

Infectious diseases are always a threat to all living beings. Today, in this world pathogens have no difficulty reaching anywhere. Every year new and deadly diseases are born and most of them are caused by viruses. Vaccines can provide lifelong immunity against infectious diseases, but the production cost of vaccines is unaffordable for a layman and traditional vaccines have certain limitations with storage and delivery. However, edible vaccines have shifted this paradigm and have received acceptance all over the world, especially in developing countries. Microalgae are one of the potential candidates for developing edible vaccines. Modifying microalgae as edible vaccines are gaining worldwide attention, especially in the world of science. Microalgae can augment the immune system as they are a promising source for antigen carriers and many of them are regarded as safe to eat. Moreover, they are a pantry of proteins, vitamins, minerals, and other secondary metabolites like alkaloids, phenols, and terpenes. In addition, being resistant to animal pathogens they are less sophisticated for genetic modification. This review analyses the potential scope of microalgae as an edible vaccine source.

Tobacco Seed-Based Oral Vaccination against Verocytotoxic O138 Escherichia coli as Alternative Approach to Antibiotics in Weaned Piglets.

Post-weaning diarrhoea and enterotoxaemia caused by Escherichia coli are serious threats in the pig (Sus scrofa domesticus) livestock industry and are responsible for economic losses related to mortality, morbidity and stunted growth. The aim of this study was to evaluate the effect of an engineered tobacco seeds-based edible vaccine in O138 Escherichia coli-challenged piglets throughout a multidisciplinary approach. Thirty-six weaned piglets were enrolled and randomly divided into two experimental groups, a control (C; n = 18) group and a tobacco edible vaccination group (T, n = 18), for 29 days of trial. At days 0, 1, 2, 5 and 14, piglets of the T group were fed with 10 g of the engineered tobacco seeds line expressing F18 and VT2eB antigens, while the C group received wild-type tobacco seeds. After 20 days, 6 piglets/group were orally challenged with the Escherichia coli O138 strain (creating four subgroups: UC = unchallenged control, CC = challenged control, UT = unchallenged tobacco, CT = challenged tobacco) and fed with a high protein diet for 3 consecutive days. Zootechnical, clinical, microbiological, histological and immunological parameters were assayed and registered during the 9 days of post-challenge follow up. At 29 days post-challenge, the CT group displayed a lower average of the sum of clinical scores compared to the CC group (p < 0.05), while the CC group showed a higher average sum of the faecal score (diarrhoea) (p < 0.05) than the CT group. A decreased number of days of shedding of the pathogenic strain was observed in the CT compared to the CC group (p < 0.05). Specific anti-F18 IgA molecules were significantly higher in the CT group compared to the CC group's faecal samples during the post-challenge period (p < 0.01). In conclusion, edible vaccination with engineered tobacco seeds showed a protective effect on clinical symptoms and diarrhoea incidence during the post-challenge period, characterized by a limited time of pathogenic strain shedding in faeces.

Edible Vaccine - An Effective Way for Immunization.

Edible vaccines are cost-effective, easy to take, storable as well as bio-friendly. If they are administered orally, they are capable of lessening the occurrence of several diseases, like HPV, Norwalk virus, as well as Polio. They are obtained by utilizing a specific portion of the plant, which results in the formulation of an attractive encoded protein. These particular encoded proteins enhance the mucosal movement along with diminishing resistance. There are different food items that are utilized in injectable antibodies, for example, wheat, rice, bananas, lettuce, potatoes, and tomatoes, which help overcome all the issues related to conventional antibodies; this demonstrates that palatable immunization is the best substitute for customary antibodies.