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Edible vaccines offer cost-effective, easily administrable, storable and widely acceptable as bio friendly particularly in developing countries. Oral administration of edible vaccines proves to be promising agents for reducing the incidence of various diseases like hepatitis and diarrhea especially in the developing world, which face the problem of storing and administering vaccines. Edible vaccines are obtained by incorporating a particular gene of interest into the plant, which produces the desirable encoded protein. Edible vaccines are specific to provide mucosal activity along with systemic immunity. Various foods that are used as alternative agents for injectable vaccines include cereals (wheat, rice, corn) fruits (bananas) and vegetables (lettuce, potatoes, tomatoes). Thus, edible vaccines overcome all the problems associated with traditional vaccines and prove to be best substitutes to traditional vaccines.
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Citation: Jan N, Sha F, bin Hameed O, Muzaffar K, Dar SM, Majid I, et al. An Overview on Edible Vaccines and
Immunization. Austin J Nutri Food Sci. 2016; 4(2): 1078.
Austin J Nutri Food Sci - Volume 4 Issue 2 - 2016
ISSN : 2381-8980 |
Nayik et al. © All rights are reserved
Austin Journal of Nutrition and Food
Open Access
Edible vaccines offer cost-effective, easily administrable, storable and
widely acceptable as bio friendly particularly in developing countries. Oral
administration of edible vaccines proves to be promising agents for reducing
the incidence of various diseases like hepatitis and diarrhea especially in the
developing world, which face the problem of storing and administering vaccines.
Edible vaccines are obtained by incorporating a particular gene of interest into
the plant, which produces the desirable encoded protein. Edible vaccines are
specic to provide mucosal activity along with systemic immunity. Various foods
that are used as alternative agents for injectable vaccines include cereals (wheat,
rice, corn) fruits (bananas) and vegetables (lettuce, potatoes, tomatoes). Thus,
edible vaccines overcome all the problems associated with traditional vaccines
and prove to be best substitutes to traditional vaccines.
Keywords: Edible vaccines; Transgenic plant; Traditional vaccines
and do not need cold-chain maintenance. Edible vaccines can be
stored at the site of use thus avoiding long-distance transportation.
Syringes and needles are also not required, thus reduces the incidence
of various infections [3]. Important advantage of edible vaccines
is elimination of contamination with animal viruses-like the mad
cow disease, which is a hazard in vaccines developed from cultured
mammalian cells, as plant viruses cannot infect humans. Edible
vaccines act by stimulating the mucosal as well as systemic immunity,
as soon they meet the digestive tract lining. is dual mechanism of
action of edible vaccines provide rst-line defense against pathogens
attacking via mucosa, like Mycobacterium tuberculosis and carriers
causing diarrhea, pneumonia, STDs, HIV etc. [1]. Oral administration
of edible vaccines to mothers might prove to be useful in immunizing
the fetus-in-utero by transplacental movement of maternal antibodies
or the infant through breast-feeding. Edible vaccines enable the
process of seroconversion in the presence of maternal antibodies,
thus playing a possible role in protecting children against diseases
like group-B Streptococcus, respiratory syncytial virus (RSV), etc. At
present edible vaccines are produced for various human and animal
diseases (measles, cholera, foot and mouth disease and hepatitis B,
C and E). ey can also be used to prevent exceptional diseases like
dengue, hookworm, rabies, etc. by combining with other vaccination
programmes enabling multiple antigen delivery. Various foods
under investigation for use in edible vaccines include banana, potato,
tomato, lettuce, rice, etc. [4].
Developing an Edible Vaccine
e selected gene obtained from the microbes encoding specic
antigen can be handled in two dierent ways:
1. Suitable plant virus is genetically engineered to produce the
desired peptides/proteins. e recombinant virus is then
incorporated into the plant, which enables it to produce a
huge number of new plants from which chimeric virions are
isolated and puried. e consequential edible plant vaccine
can then be used for immunological applications.
2. In another method, the desirable gene is incorporated with
Vaccines have proved to be boon for the prevention of infectious
diseases. In spite of the global immunization programme for children
against the six devastating diseases, 20% of infants still remain un-
immunized which lead to approximately two million unnecessary
deaths per annum, particularly in the far ung and poor parts of the
world [1]. is is because of the limitations on vaccine production,
distribution and delivery. is problem needs to resolve in order to
prevent the spread of infections and epidemics by un-immunized
populations in the immunized, safe areas [2]. Immunization for
certain infectious diseases, either do not exist or they are unreliable
or very expensive like; immunization via DNA vaccines is substitute
but is an expensive method, along with some undesirable immune
responses. Besides being expensive, these vaccines pose the problem
of storage and transportation, as many of them require refrigeration.
Hence, there is search for easily administrable, storable, fail-safe and
widely acceptable bio friendly vaccines and their delivery systems
especially in developing countries. erefore, as substitutes have to be
produced for traditional vaccines, it was envisaged that plants could
be promising agents for ecient production system for vaccines,
which in turn gave rise to the novel concept of edible vaccines.
Concept of Edible Vaccines
Development of edible vaccines involves the process of
incorporating the selected desired genes into plants and then
enabling these altered plants to produce the encoded proteins. is
process is known as transformation, and the altered plants are known
as transgenic plants. Edible vaccines like traditional subunit vaccines
consist of antigenic proteins and are devoid of pathogenic genes.
Despite this advantage, traditional subunit vaccines are unaordable
and technology-intensive, require purication, refrigeration and
produce poor mucosal response. Unlikely, edible vaccines would
eliminate the need for trained medical personnel required for oral
administration particularly in children. Production of edible vaccines
is eective process and can be easily scaled up. Edible vaccines oer
numerous advantages like they posses good genetic and heat stability
Review Article
An Overview on Edible Vaccines and Immunization
Naeema Jan1, Fouzia Sha1, Omar bin Hameed1,
Khalid Muzaffar2, Shuaib Mohammad Dar2,
Ishrat Majid2 and Nayik GA2*
1Division of Post Harvest Technology, SKUAST-Kashmir,
2Department of Food Engineering & Technology, SLIET,
Punjab, India
*Corresponding author: Nayik GA, Department of
Food Engineering & Technology, SLIET, Punjab, India
Received: March 03, 2016; Accepted: June 01, 2016;
Published: June 07, 2016
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Nayik GA Austin Publishing Group
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plant vector by transformation. Many other approaches have
been utilized which can be categorized into following groups:
Agrobacterium mediated gene transfer
In this method, the suitable gene (recombinant DNA) is
incorporated into the T‐region of a disarmed Ti plasmid of
Agrobacterium; a plant pathogen, which is co-cultured with the plant
cells, or tissues that needs to be transformed (Figure 1). is approach
is slow with lower yield however; it showed satisfactory results in
dicotelydenous plants like potato, tomato and tobacco. Researches
in some elds have proven this approach good in expressing the
desirable traits by selected genes in several experimental animals and
plants [5,6].
Biolistic method
is sophisticated method involves the use of gene gun that
res the gene containing DNA coated metal (e.g. gold, tungsten)
particles at the plant cells [7]. Plant cells are then permitted to grow
in new plants, which are later on cloned to produce ample number
of crop with similar genetic composition. is approach is highly
attractive due to its undependability on regeneration ability of the
species as DNA is directly incorporated into cells of plant. However,
requirement of expensive device particle gun adds to the major
drawback to this method.
In this method DNA is inserted into the cells aer which they are
exposed to high voltage electrical pulse which is believed to produce
transient pores within the plasma lemma. is approach requires the
additional eort of weakening the cell wall as it acts as an eective
barrier against entry of DNA into cell cytoplasm hence, it requires
mild enzymatic treatment.
Mechanism of Action
Since almost all human pathogens invade at mucosal surfaces
via urogenital, respiratory and gastrointestinal tracts as their leading
path of entry into the body. us, foremost and prime line of the
defense mechanism is mucosal immunity [8]. e most ecient
path of mucosal immunization is oral route because oral vaccines
are able to produce mucosal immunity, antibody mediated immune
response and cell mediated immune response. As an advantage
orally administered antigen containing plant vaccine do not get
hydrolysed by gastric enzymes due to tough outer wall of the plant
cell. Transgenic plants containing antigens act by the process of bio-
encapsulation, i.e., outer rigid cell wall and are nally hydrolysed and
released in the intestines. e released antigens are taken up by M
cells in the intestinal lining that are placed on Payer’s patches and
gut-associated lymphoid tissue (GALT). ese are further passed on
to macrophages and locallymphocyte populations, producing serum
IgG, IgE responses, local IgA response and memory cells, that rapidly
counterbalance the attack by the real infectious agent [1] (Figure 2).
Advantages of Edible Vaccines
1. Edible vaccines have ecient mode of action for immunization,
as they do not require subsidiary elements to stimulate immune
2. Edible vaccine unlike traditional vaccines brings forth mucosal
3. Edible vaccines are comparatively cost eective, as they do not
require cold chain storage like traditional vaccines [9].
4. Edible vaccines oer greater storage opportunities as they seeds
of transgenic plants contain lesser moisture content and can be easily
dried. In addition, plants with oil or their aqueous extracts possess
more storage opportunities [10].
5. Edible vaccines do not need sophisticated equipments and
machines as they could be easily grown on rich soils and the method
is economical compared to cell culture grown in fermenters.
6. Edible vaccines are widely accepted as they are orally
administered unlike traditional vaccines that are injectable. us,
they eliminate the requirement of trained medical personnel and the
risk of contamination is reduced as they do not need premises and
manufacturing area to be sterilized [11].
7. Edible vaccines oer greater opportunity for second-generation
vaccines by integrating numerous antigens, which approach M cells
8. Edible vaccines are safe as they do not contain heat-killed
pathogens and hence do not present any risk of proteins to reform
into infectious organism.
9. Edible vaccine production process can be scaled up rapidly by
Limitations of Edible Vaccines
Following are some major drawbacks of edible vaccines,
Figure 1: Development of edible vaccines from potato.
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• Individual may develop immune tolerance to the particular
vaccine protein or peptide.
• Dosage required varies from generation to generation and,
plant to plant, protein content, patient is age, weight, ripeness
of the fruit and quantity of the food eaten.
• Edible vaccine administration requires methods for
standardization of plant material/product as low doses may
produce lesser number of antibodies and high doses are
responsible immune tolerance.
• Edible vaccines are dependent on plant stability as certain
foods cannot be eaten raw (e.g. potato) and needs cooking
that cause denaturation or weaken the protein present in it
• Edible vaccines are prone to get microbial infestation e.g.
potatoes containing vaccine can last long if stored at 4oC
while a tomato cannot last long.
• Proper demarcation line is necessary y between ‘vaccine fruit’
and ‘normal fruit’ to avoid misadministration of vaccine,
which can lead to vaccine tolerance.
• Edible vaccine function can be hampered due to vast
dierences in the glycosylation pattern of plants and humans.
General challenges
Many dierent challenges are confronted before developing a
plant-based vaccine. However, it has been proved in three successful
human clinical trials that sucient doses of antigen can be achieved
with plant-based vaccines [11]. But, to determine dose, following
considerations need to be born in mind viz. person’s weight, age;
fruit/plants size, ripeness and protein content. e quantity to be
eaten is important, particularly in infants, who might spit it, eat
only a part or eat it whole and throw it up aerwards. Lesser dosage
fails to produce sucient antibodies, and higher dosage may lead to
tolerance. Practically it would be more appropriate to concentrate the
vaccine into a teaspoonful of baby food rather than incorporating it
in a whole fruit. e transgenic plants can further be made available
in various shapes like; pills, puddings, chips, etc. Trials to enhance
the quantity of antigens produced present a challenge in the form of
under developed growth of plants and reduced tuber/fruit formation,
because many m-RNA from the transgene lead to gene-silencing in
plant genome.
One of the approaches to overcome above mentioned challenges
is listed as follows:
Expressing the plant nuclear genetic material in; plastids [13]
foreign genes [14] fused protein coats [15] and by standardizing and
optimizing the coding sequence of bacterial/viral genes.
Non scientic challenges
Albeit, edible vaccine production is focused in the developing
countries, which is basic, reason of poor research in this eld because
smaller organizations invest in it as larger companies are engaged
in livestock market than human application. Also very, few number
of international and local government organizations support which
mostly remains underfunded. Many of the organizations have lost
interest in edible vaccines research due to unavailability of investors,
assurance in returns on investments, grants, research aid and nancial
support. Also the already available inject able vaccines for diseases
like tetanus, diphtheria etc. provide lesser opportunity to develop
edible vaccines for them as recombinant vaccines are so cheap now.
Examples of Edible Vaccines
Transgenic potatoes for diarrhea
e rst successful human trial for an edible vaccine was conducted
in year 1997 in which volunteers were fed transgenic potatoes, which
possessed the b-subunit of the E. coli heat-labile toxin, responsible for
diarrhea. A 4-fold increase in serum antibodies 1999 was manifested
in ten out of the 11 volunteers [1]. Next clinical trial took place at the
Boyce ompson Institute at Cornell University, USA, in which 20
volunteers ate the potatoes containing the Norwalk virus (responsible
for vomiting and diarrhea), out of which19 showed an immune
response [1]. Potato-based edible vaccine has a major drawback that
it needs to be eaten as raw because cooking causes denaturation of
protein and makes it uneective.
Transgenic tomatoes against diarrhea
Transgenic tomatoes were produced at the Cornell University,
in the US, against the Norwalk virus, responsible agent for severe
diarrhea. e transgenic tomatoes are capable to produce surface
protein specic to the virus and it has been shown that mice fed with
transgenic tomatoes showed an immune response towards the virus.
Figure 2: Mechanism action of edible vaccines produced from potato.
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Other transgenic plants
Presently, banana is being exploited as a good source for edible
vaccine production because of it’s two major advantages it does not
require cooking and is locally grown plant. However, the protein
expression in transgenic banana is tissue specic promoter dependent.
Several other examples involve rabies glycoprotein expressed by viral
vectors in spinach [16] and hepatitis B surface antigen in case of
lettuce and potato [17].
Cancer therapy
Several plants have been successfully engineered to generate
monoclonal antibodies that have been veried as eective cancer
therapy agents. One example is that of monoclonal body in case
of soyabean (BR-96) is an ecient agent that attacks doxorubicin
responsible for breast cancer, ovarian cancer, colon cancer and lung
tumors [18].
Birth control
Administration of TMV produces protein that is found in
Mousezona pellucida (ZB3 protein) and is capable of preventing
fertilization of eggs in mice due to resulting antibodies [18].
Chloroplast transformation
As the chloroplast genome cannot be transmitted with in crops
via usual cross pollination due to its nature of maternal inheritance
[19]. It may contribute to its transmission as well as accumulation in
ample quantities in the form of transgenic protein.
Role in autoimmune diseases
In concern with autoimmune diseases, scaling up of self- antigen
production in plants is underway in it’s developmental stage. Few
of the diseases that are under study include; multiple sclerosis,
rheumatoid arthritis, lupus and transplant rejection. In one clinical
study strain of mouse susceptible to diabetes were fed with potatoes
capable of expressing insulin and a protein called GAD (glutamic acid
decarboxylase), linked to CT-B subunit. It has been found out that the
protein proved successful in suppressing immune attack and delayed
the onset of high blood sugar level [8].
Recombinant drugs/proteins
Besides, being major producers of vaccines and antibodies,
plant compositions are altered by engineered viral inoculations to
produce enzymes; drugs (albumin, serum protease and interferon)
e.g. glucocerebrosidase (hGC) production in tobacco plants for
treating Gaucher’s disease, Interleukin-10 to treat Crohn’s disease
is method of production is quite cheaper and reduces the cost by
thousand-fold [20]. e process of recombinant therapeutic protein
production from plants has been commercialized as hirudin which
is an antithrombin-anti-viral protein that inhibits the HIV virus
in vitro, trichosanthin(ribosome in activator) and angiotensin-I
(antihypersensitive drug) [20].
The Future of Edible Vaccines
Resistance towards GM foods presents a threat to the rising
future of edible vaccines. Transgenic contamination is also a major
concern which need to be addressed properly as it led United States
to pay o approximately $12 billion. Edible vaccines before launching
in market for human applications require certication by WHO in
terms of it’s quality, eciency and environmental eect. Despite
above concerns the future of edible vaccines is reected by enormous
increase in land area used for cultivation of transgenic crops from
1.7 to 44.2 million hectares from 1996 to 2000. Also the number
of countries growing them increased from 6 to 13 which predicted
that transgenic crops gained wide acceptance industrially as well as
in developing countries. Edible vaccines present good economical
and technological benets as more than 350 genetically engineered
products are presently in progress in the United States and Canada.
In the near future edible vaccine against smallpox, anthrax, plague,
etc can be produced on a large scale (upto millions of doses) within a
short span of time.
Edible plant-derived vaccines present a better possibility of safer
and more ecient immunization in the future. Limitations linked
with traditional vaccines, like production, distribution and delivery
can be eliminated by the use of edible vaccines through various
immunization programmes. Edible vaccines successfully embraced
the obstacles encountered in rising vaccine technology. Despite
restricted global access to health care and much attention still being
paid towards complex diseases like HIV, malaria, etc. e time is
not so far when there is need for an economical, safer and ecient
delivery system to be developed at a larger scale in the form of edible
vaccines e ray of hope is based on assumption that edible vaccines
may be grown mostly in the developing countries which is basically a
fact as in reality they would be used in these countries. Hence, edible
vaccines provide a greater opportunity in the near future when no
longer injectable needles be used but a fruitful path may be available
where an individual get protected from diseases by simply eating a
e rst author is very much thankful to Ishrat Majid doctoral
fellow at Department of Food Engineering & Technology, SLIET
Longowal, Punjab, India for helping in writing this article.
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Citation: Jan N, Sha F, bin Hameed O, Muzaffar K, Dar SM, Majid I, et al. An Overview on Edible Vaccines and
Immunization. Austin J Nutri Food Sci. 2016; 4(2): 1078.
Austin J Nutri Food Sci - Volume 4 Issue 2 - 2016
ISSN : 2381-8980 |
Nayik et al. © All rights are reserved
... From 1996 to 2000, about 1.7 to 44.2 million hectares of land used for growing transgenic crops and the future of edible vaccines is revealed by this massive increase. The number of countries farming them increased from 6 to 13, indicating that transgenic crops are gaining widespread approval in both developed and developing countries (Jan et al., 2016). The majority of the edible vaccines were against viruses and bacteria that cause a deadly infection in humans, animals, as well as in poultry. ...
... This is due to the difficulties in the production, distribution, and delivery of vaccine. We need to deal with this problem of the unvaccinated population to prevent the spread of diseases and epidemics (Jan et al., 2016). According to the literature (Ramsay et al., 1999), 100 % vaccination is required. ...
... Vaccines can be used as an alternative, but the process is costly, and some people may not want to use it. Immune reactions that are not ideal arise (Jan et al., 2016). Aside from being a costly methodology, the storage and transportation of vaccines is another issue. ...
Full-text available
The researchers are still doing efforts to develop an effective, reliable, and easily accessible vaccine candidate to protect against COVID‐19. As of the August 2020, nearly 30 conventional vaccines have been emerged in clinical trials, and more than 200 vaccines are in various development stages. Nowadays, plants are also considered as a potential source for the production of monoclonal antibodies, vaccines, drugs, immunomodulatory proteins, as well as used as bioreactors or factories for their bulk production. The scientific evidences enlighten that plants are the rich source of oral vaccines, which can be given either by eating the edible parts of plants and/or by oral administration of highly refined proteins. The use of plant‐based edible vaccines is an emerging trend as it possesses minimum or no side effects compared with synthetic vaccines. This review article gives insights into different types of vaccines, the use of edible vaccines, advantages of edible vaccines over conventional vaccines, and mechanism of action of edible vaccines. This review article also focuses on the applications of edible vaccines in wide‐range of human diseases especially against COVID‐19 with emphasis on future perspectives of the use of edible vaccines.
... However, softening of the cell wall is also needed as it acts as a barrier for the entry of DNA into the cytoplasm. Hence, mild enzymatic treatment is given to the cells (Jan et al., 2016;Munshi & Sharma, 2018). ...
... In a similar approach, live bacteria can be bio-engineered to ex- | 11 mucosal surface. Mucosal immunity becomes the first and most essential line of defence as the lining of all the tracts is formed by mucosa (Jan et al., 2016). Immunization of the mucosal defence system might be effective for the prevention or protection from various diseases and the most appropriate approach to boosting the mucosal immunity is the oral route ( Figure 1). ...
Vaccination is the most suitable and persuasive health care program for the prohibition of various deadly diseases. However, the higher production cost and purification strategies are out of reach for the developing nations. In this scenario, development of edible vaccine turns out to be the most promising alternative for remodeling the pharmaceutical industry with reduced production and purification costs. Generally, oral route of vaccination is mostly preferred due to its safety, compliance, low manufacturing cost and most importantly the ability to induce immunity in both systemic and mucosal sites. Genetically modified microorganisms and plants could efficiently be used as vehicles for edible vaccines. Edible vaccines are supposed to reduce the risk associated with traditional vaccines. Currently, oral vaccines are available in the market for several viral and bacterial diseases like cholera, hepatitis B, malaria, rabies etc. Herein, the review focuses on the breakthrough events in the area of edible vaccines associated with dietary microbes and plants for better control over diseases. This article is protected by copyright. All rights reserved.
... The idea of edible vaccines is not new -it has been around for decades (Jan et al. 2016). The first reported vaccine antigen expressed in a microalga dates back to 2003 (Sun et al. 2003). ...
... Nevertheless, the fact that humans and plants belong to different kingdoms can't be altered and hence differences in modification patterns can obstruct vaccine function or at worst result in immunotolerance. Furthermore, certain antigenic biomolecules can not be well expressed in plants due to toxicity while others can result in the silencing of plant genes (Jan et al., 2016). The said challenges have been subjugated by localization of foreign genes in cell organelles (plastids, ER) or nucleus, fusing genes, codon optimization, selecting strong promoters, effective UTRs, employing transient expression systems, etc (Huy et al., 2012). ...
The current pandemic has made us realize the importance of efficient and large-scale vaccine production and distribution. Conventional vaccines have not only helped us overcome this pandemic but aided us in avoiding numerous pathogenic diseases. The production complexity and high cost of traditional vaccines have taken a toll on the world economy. Plant-derived vaccines serve to eliminate such concerns. Specifically, rice and potato being staple crops have been used extensively for the same. In this study, we have thoroughly reviewed the existing literature on rice and potato-derived edible vaccines. We have elaborated the studies performed by several researchers since 1995 for various diseases like dengue, cervical cancer, hepatitis B, diarrhea, cedar pollinosis, periodontitis, Japanese encephalitis etc. Although numerous plants such as banana, tomato, tobacco, lettuce, alfalfa, etc have been used for the production of edible vaccines, this review solely focuses on potato and rice based studies.
... Edible vaccines have various applications in the prevention of malaria, cholera, anthrax, autoimmune diseases etc. At present edible vaccines are being developed for humans and animals (Jan et al. 2016). This new technology hopefully will contribute toward the global vaccine programs and have a dramatic impact on health care in developing countries. ...
Full-text available
Vaccines are natural agents that improve insusceptibility to specific illnesses. It contains a protein that looks like a disease-causing microorganism which is made by heat killed or live attenuated microbes. Vaccines stimulate the immune reaction once it is administrated inside the body. A new form of vaccine is available these days which was produced from genetically engineered plants. These are known as edible vaccines. Edible vaccines are formed by inserting the desired gene into selected plant cell. Gene insertion can be done by direct gene delivery or indirect gene delivery method. For this reason a variety of plants and other microbes are utilized. Oral delivery of edible vaccines abolishes the usage of syringes. By encountering the host organism they tend to stimulate mucosal with systemic immunity once they are administrated. Currently, eatable vaccines are developed for several animal as well as human diseases and many of them are in experimental trials. However the major challenge experienced by edible vaccine is its recognition by the people moreover to facilitate so that it is essential to formulate awareness among the society regarding its utilization and benefits. They are inexpensive, competent, and safe for usage, need no refrigeration for storage and easily administrated. It assures an improved anticipation from diseases. Edible vaccines are developed for many diseases like malaria, hepatitis etc. This chapter sheds light on the concept of edible vaccines, different sources and approaches of their production along with their mode of action, advantages and limitations.
... They have many advantages compared with traditional vaccines, such as lower manufacturing cost and side effects 23 . The production of traditional vaccines is very expensive and limited in most countries, but in contrast, the production, purification, sterilization, and distribution of edible vaccines are easier 24 . However, they have also some limitations because edible vaccines are still new and in development and more researches must be done before widespread human usage 21 ...
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The aim of this study was to present and evaluate novel oral vaccines, based on self-amplifying RNA lipid nanparticles (saRNA LNPs), saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum, to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants alpha and delta. After invitro evaluation of the oral vaccines on HEK293T/17 cells, we found that saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum could express S-protein at both mRNA and protein levels. In the next step, BALB/c mice were orally vaccinated with saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum at weeks 1 and 3. Importantly, a high titer of IgG and IgA was observed by all of them, sharply in week 6 (P < 0.05). In all study groups, their ratio of IgG2a/IgG1 was upper 1, indicating Th1-biased responses. Wild-type viral neutralization assay showed that the secreted antibodies in vaccinated mice and recovered COVID-19 patients could neutralize SARS-COV-2 variants alpha and delta. After oral administration of oral vaccines, biodistribution assay was done. It was found that all of them had the same biodistribution pattern. The highest concentration of S-protein was seen in the small intestine, followed by the large intestine and liver.
... present such benefits, but microalgae grow faster and with more control in bioreactors; they are easier to transform, and their entire biomass can be consumed, making them a more suitable organism for oral vaccine production. The idea of edible vaccines is not new -it has been around for decades (Jan et al. 2016). The first reported vaccine antigen expressed in a microalga dates back to 2003 (Sun et al. 2003). ...
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Nutraceutical and functional foods are seen as those natural bioactive chemical compounds able to provide both health benefits to reduce the risk of chronic diseases and nutrition. This new group of products promises to be the solution to many health problems. Though both microalgae and seaweeds have been in the human diet for thousands of years, only in recent years with the new technological outcomes has the algal nutraceutical potential been reported. Algae could play an important role in the increasing the commercial value of the functional foods market. This chapter presents an overview of the main molecules that have been recovered from microalgae and seaweeds and their nutraceutical benefits and applications.
Vaccines play a vital role in the prevention of many infectious diseases. The conventional methods of vaccine production and vaccination have certain obstacles. The concept of edible vaccines came into existence in the 1990s with the thought of overcoming the obstacles of the conventional method. The rDNA technology, particularly Agrobacterium-based transformation of plant cells is employed in the production of edible vaccines. Commercial crops such as banana, potato, rice, tomato spinach, and others have been genetically modified to express the antigen capable of eliciting an immune response. There is so much research progress in developing edible vaccines against pathogenic diseases such as measles, hepatitis B, diphtheria, tetanus, acute gastrointestinal illness, AIDS, anthrax, and cholera. Research on the second-generation edible vaccines in terms of multi-subunit antigen proteins targeting more than one disease simultaneously has also been initiated. Despite there are many advantages, edible vaccines are not without any limitations. There is hope for overcoming these limitations and in the future days, edible vaccines will be an effective strategy in the mass eradication of infectious diseases.
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We previously demonstrated that recombinant plant virus particles containing a chimeric peptide representing two rabies virus epitopes stimulate virus neutralizing antibody synthesis in immunized mice. We show here that mice immunized intraperitoneally or orally (by gastric intubation or by feeding on virus-infected spinach leaves) with engineered plant virus particles containing rabies antigen mount a local and systemic immune response. After the third dose of antigen, given intraperitoneally, 40% of the mice were protected against challenge infection with a lethal dose of rabies virus. Oral administration of the antigen stimulated serum IgG and IgA synthesis and ameliorated the clinical signs caused by intranasal infection with an attenuated rabies virus strain.
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Plants have considerable potential for the production of biopharmaceutical proteins and peptides because they are easily transformed and provide a cheap source of protein. Several biotechnology companies are now actively developing, field testing, and patenting plant expression systems, while clinical trials are proceeding on the first biopharmaceuticals derived from them. One transgenic plant-derived biopharmaceutical, hirudin, is now being commercially produced in Canada for the first time. Product purification is potentially an expensive process, and various methods are currently being developed to overcome this problem, including oleosin-fusion technology, which allows extraction with oil bodies. In some cases, delivery of a biopharmaceutical product by direct ingestion of the modified plant potentially removes the need for purification. Such biopharmaceuticals and edible vaccines can be stored and distributed as seeds, tubers, or fruits, making immunization programs in developing countries cheaper and potentially easier to administer. Some of the most expensive biopharmaceuticals of restricted availability, such as glucocerebrosidase, could become much cheaper and more plentiful through production in transgenic plants.
It is estimated that one-third of all prescription drugs on markets around the world are originally derived from plants, although most are now synthetic analogues of chemicals found in plants. With the advent of genetic engineering, plants may again stage a comeback but now as a novel source of preventive drugs. Transgenic plants producing antigens against cholera, hepatitis B and rabies have been developed in US laboratories.
Oral administration of disease-specific autoantigens can prevent or delay the onset of autoimmune disease symptoms. We have generated transgenic potato plants that synthesize human insulin, a major insulin-dependent diabetes mellitus autoantigen, at levels up to 0.05% of total soluble protein. To direct delivery of plant-synthesized insulin to the gut-associated lymphoid tissues, insulin was linked to the C-terminus of the cholera toxin B subunit (CTB). Transgenic potato tubers produced 0.1% of total soluble protein as the pentameric CTB-insulin fusion, which retained GM1-ganglioside binding affinity and native antigenicity of both CTB and insulin. Nonobese diabetic mice fed transformed potato tuber tissues containing microgram amounts of the CTB-insulin fusion protein showed a substantial reduction in pancreatic islet inflammation (insulitis), and a delay in the progression of clinical diabetes. Feeding transgenic potato tissues producing insulin or CTB protein alone did not provide a significant reduction in insulitis or diabetic symptoms. The experimental results indicate that food plants are feasible production and delivery systems for immunotolerization against this T cell-mediated autoimmune disease.
Human immunodeficiency virus (HIV)—infected persons may be important, unrecognized transmitters of measles virus, thwarting eradication efforts. We reviewed the published English-language literature on measles and measles immunization in HIV-infected persons to investigate the clinical features of measles, the responses to measles immunization, and the safety of measles vaccine in HIV-infected persons and, conversely, the effect of measles and measles immunization on HIV infection. HIV-infected persons with measles are likely to have uncharacteristic clinical findings and severe illness, with high rates of pneumonitis and death. Primary and secondary failure of measles vaccine in HIV-infected children may permit transmission of measles virus in spite of high rates of immunization coverage. A factor that complicates measles-control efforts in areas of high prevalence of HIV is the potential for fatal infection with measles vaccine virus. Further research on the impact of the HIV epidemic on measles and measles immunization is necessary to guide strategies for the eradication of measles.
In this article, we describe several novel genetic vaccination strategies designed to facilitate the development of different types of immune responses. These include: i) the consecutive use of DNA and fowlpoxvirus vectors in "prime-boost" strategies which induce greatly enhanced and sustained levels of both cell-mediated immunity and humoral immunity, including mucosal responses; ii) the co-expression of genes encoding cytokines and cell-surface receptors, and the use of immunogenic carrier molecules, for immune modulation and/or improved targeting of vector-expressed vaccine antigens; and iii) the expression of minimal immunogenic amino acid sequences, particularly cytotoxic CD8+ T-cell determinants, in "polytope" vector vaccines. The capacity to modulate and enhance specific immune responses by the use of approaches such as these may underpin the development of vaccines against diseases for which no effective strategies are currently available.
One day children may get immunized by munching on foods instead of enduring shots. More important, food vaccines might save millions who now die for lack of access to traditional inoculants
Here we present data showing oral immunogenicity of recombinant hepatitis B surface antigen (HBsAg) in preclinical animal trials. Mice fed transgenic HBsAg potato tubers showed a primary immune response (increases in HBsAg-specific serum antibody) that could be greatly boosted by intraperitoneal delivery of a single subimmunogenic dose of commercial HBsAg vaccine, indicating that plants expressing HBsAg in edible tissues may be a new means for oral hepatitis B immunization. However, attainment of such a goal will require higher HBsAg expression than was observed for the potatoes used in this study. We conducted a systematic analysis of factors influencing the accumulation of HBsAg in transgenic potato, including 5' and 3' flanking elements and protein targeting within plant cells. The most striking improvements resulted from (1) alternative polyadenylation signals, and (2) fusion proteins containing targeting signals designed to enhance integration or retention of HBsAg in the endoplasmic reticulum (ER) of plant cells.
Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis with over 180 million cases worldwide. Vaccine development for HCV has been difficult. Presently, the virus cannot be grown in tissue culture and there is no vaccine or effective therapy against this virus. In this research, we describe the development of an experimental plant-derived subunit vaccine against HCV. A tobamoviral vector was engineered to encode a consensus sequence of hypervariable region 1 (HVR1), a potential neutralizing epitope of HCV, genetically fused to the C-terminal of the B subunit of cholera toxin (CTB). This epitope was selected from among the amino acid sequences of HVR1 "mimotopes" previously derived by phage display technology. The nucleotide sequence encoding this epitope was designed utilizing optimal plant codons. This mimotope is capable of inducing cross-neutralizing antibodies against different variants of the virus. Plants infected with recombinant tobacco mosaic virus (TMV) engineered to express the HVR1/CTB chimeric protein, contained intact TMV particles and produced the HVR1 consensus peptide fused to the functionally active, pentameric B subunit of cholera toxin. Plant-derived HVR1/CTB reacted with HVR1-specific monoclonal antibodies and immune sera from individuals infected with virus from four of the major genotypes of HCV. Intranasal immunization of mice with a crude plant extract containing the recombinant HVR1/CTB protein elicited both anti-CTB serum antibody and anti-HVR1 serum antibody which specifically bound to HCV virus-like particles. Using plant-virus transient expression to produce this unique chimeric antigen will facilitate the development and production of an experimental HCV vaccine. A plant-derived recombinant HCV vaccine can potentially reduce expenses normally associated with production and delivery of conventional vaccines.