Note : This story was published in CSIR-NISCAIR’s prestigious magazine ‘ Science Reporter’ in June 2021.
If you are given a choice for vaccination –
You want to have the vaccine injected in your body with a syringe?
You want to get vaccinated with some nasal spray?
You want to swallow the vaccine with a few sips of water?
What will you choose? Many of us will straightaway choose the third or second option.
But wait. Vaccines are not like a simple medicine. Rather they are like an armour for our internal body to be protected from deadly viruses. So, its impact on our body should be the most important consideration while making a choice. A key vaccine should hamper multiplication and spread of virus. Till now no available vaccine controls virus infection the way it is supposed to be.
For the deadly coronavirus forcing us to lockdowns, curfews, masks and sanitizers all over again, oral vaccines are the new challenge. The journey has just begun… Scientists are on their job 24*7… and as per experts it will take almost an year or so for the oral vaccines to reach us, and we have hopes in our minds and souls. This hope has been ignited by a few players in the new drug delivery system arena.
Oral Vaccine Capsule
Latest to mention is an effort made by Oravax Medical, a joint venture of Gurugram-based biotechnology firm Premas Biotech and Oramed Pharmaceuticals, a company headquartered in Jerusalem… The process of oral vaccine development is in preliminary stage… Premas Biotech has a full fledged faculty consisting of scores of scientists specialising in different streams… Whenever a vaccine is developed, it goes through different phases… Like any other vaccine trial, Oral Vaccines are also first tested on animals like mice, rabbits or monkeys… The human trial is done at final stages and is subject to very stringent ethical norms, and medical regulations. Here, good news is that this Oral COVID-19 Vaccine ‘Oravax’ candidate produced antibodies after a single dose in pilot animal studies. Clinical trials will begin soon.
How Oral Vaccine Capsule is made?
These oral capsules are soft gel capsules, and they are manufactured in a specialized set up. They cannot be manufactured in the lab, but in a special machine that combines the materials and encloses them in a soft gel capsule.
Oral vaccine capsules provides triple protection against Covid-19 by destroying three parts of the virus: Spike, membrane, and envelope targets.
How the oral vaccines Capsule work in our body?
Oral vaccines or any vaccine for it to be functional, has to perform its role, i.e. promote a robust immune response, and that immune response is protective. Oral vaccines as a method of delivery has not been so successful except for oral polio vaccine. So, the nature of the problem is to be able to avoid the acid of the stomach and the proteases in the small intestine. The small intestine or the gut in humans has its own set of immune cells and offers protection and immunity. For this we are in a wait and watch situation.
Intranasal Vaccine
Another oral vaccine in clinical trials now is the intranasal vaccine. To protect ourselves from the deadly coronavirus, the whole world relies on wearing masks… Reason being the virus enter the body through our nasal cavity and mouth… So, nasal tract is the most crucial area of attack by coronavirus. So, an intranasal vaccine is given through the nose, and it delivers the dose directly to the respiratory pathway, much like a nasal spray. Bharat Biotech is in licensing agreement with Washington University School of Medicine in St. Louis for a novel chimp- adenovirus, single dose intranasal vaccine for COVID-19. It is the first intranasal vaccine for COVID-19 and is already undergoing clinical trials. Thus nasal sprays are a ray of hope for effective vaccine.
How Intranasal Vaccine works ?
This is important to understand that immune responses at the site of infection i.e. in the nasal mucosa is essential for blocking both infection and transmission of COVID-19… And the Intranasal Vaccine is believed to do this efficiently by stimulating a broad immune response. When it is given through the nose, it gets absorbed in the mucus membrane, present in the upper throat where the absorption is much faster… It helps develop an immune response in the nose and develop antibodies… All these help not only prevent the infection but also killing the virus at the entry point and not allowing to hamper any of our body system… The intranasal vaccine requires only a single dose of 0.1 ml, using a spray in each of the nostrils…
Animal trials for Intranasal Vaccine
The trials in mice, Hamsters and Rhesus Macaques with single dose of intranasal vaccine conferred protection against SARS CoV2… Observations of animal trails showed clear lower and upper airways of respiratory tract from virus… The nasal route is an excellent way for vaccination as it is the entry point for the virus… It blocks the disease carrier and stops transmission of infection then and there… In India, the human stage trials for nasal vaccines have begun. Also, the results observed till now can vary for humans and overall. So, we need to wait for the final conclusions…
Intranasal vaccine VS Capsule vaccine : Which is more effective ?
Because of better compliance both the intranasal and oral immunization routes are attractive. Nasal immunization leads to induction of immune responses in the local nasal, adjacent oral and the distant mucosal sites. It induces a stronger mucosal response that can protect against the infection at the mucosal surfaces. Whereas oral immunization generates immune response in the gut. The mechanism of antigen processing and presentation by antigen presenting cells and the process of antibody generation, may not be very different between nasal and oral immunization. Importantly, responses in oral immunization are also good like in nasal immunization but they may not be as effective as nasal immunization when it comes to protection in the local nasal sites or respiratory tract.
Nimesh Gupta, Head of Vaccine Immunology Laboratory at National Institute of Immunology under Department of Biotechnology opines that “In the context of SARS-CoV-2 vaccine, the nasal immunization may be effective in controlling the virus replication in the upper respiratory tract and thereby, may control the spread of COVID virus. This is exactly what we need now to control the pandemic. Of course, a better immunological understanding of correlates of protection in the upper respiratory tract will be required for the assessment and implementation of such nasal vaccines”.
We always talk about effectiveness of a vaccine, so let’s also explore how to make vaccine (Injectable/Oral-Intranasal or Capsule) effective on deadly virus? Nimesh Gupta adds – “To make an effective vaccine we should know where to hit on the virus that could restrict virus entry into the cells and its dissemination. Once we know the target of the virus, then we should know what kind and magnitude of immune response is required to confer a long-lasting protective immunity against this identified target. Next goal will be to achieve similar immune responses using a vaccine formulation. This is how a rational and effective vaccine could be developed against the complex virus”.
Benefits of Oral Vaccine
Oral vaccines
- will encourage a large population to get vaccinated,
- will cut off the need of freezing temperature for transport and storage,
- are easy to distribute and administer anytime, anywhere,
- will negate the need to carry two rounds of vaccine administrations,
- will lower the cost of administration and delivery of vaccine as associated costs will not be there, like syringes, swabs, ultra-cold freezers, etc.
- does not require trained health care workers,
- will eliminate needle-associated risks (injuries and infections),
- will quickly vaccinate the most vulnerable and people in remote areas,
- will be convenient for all ages,
- benefits especially those who fear needles
Challenges for Oral Vaccine
- Most crucial challenge with developing an oral vaccine is that gastric juices would rapidly degrade any protective layers enclosing the antigen and make the vaccine useless.
- Oral vaccines must have formulations to overcome the harsh gastrointestinal (GI) environment
- Oral vaccines must avoid tolerance induction to achieve effective protection.
Unanswered questions :
- Will Oral Vaccine be able to work on virus mutations?
- Will Oral Vaccine have the efficacy, at least, similar to the current coronavirus injectables?
- Will Oral Vaccine be universal in nature, i.e. effective on all strains?
- Will the Oral Vaccines be effective on all age groups?
- Will Oral Vaccines be given to children as well?
No doubt oral vaccine in either way is the most patient friendly route, but there are unanswered questions. For any Vaccine, its efficacy is the most serious concern. It is believed that Oral vaccines, whether living or non-living, viral or bacterial, elicit diminished immune responses or have lower efficacy. And as our experts clearly indicate it is too early to come to conclusions. But, we know science has taken a leap. What was not possible a few years back is possible now, continues to develop in future and will remain forever.
EXPERTS ON ORAL VACCINE
Dr. Gagandeep Kang, Renowned Vaccine Scientist, Professor of Microbiology, Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College (CMC), Vellore
“We need multiple vaccines given the scale of the pandemic and the large population of our country who needs to be vaccinated. Indigenous vaccine development is a welcome step and will help in addressing the current pandemic and also serve in building capacity for future. Innovations are the need of the day and oral vaccines for SARS-CoV-2 if successful and approved through established regulatory processes, will be beneficial, as they will enable better vaccine compliance.”
Dr. Soumya Swaminathan, Chief Scientist, World Health Organisation
It’s too early to judge. But good to test more vaccines especially oral ones, in clinical trials.
Dr. Shekhar C Mande, Director, Council of Scientific and Industrial Research
“We need multiple vaccines given the scale of the pandemic and the large population of our country who needs to be vaccinated. Indigenous vaccine development is a welcome step and will help in addressing the current pandemic and also serve in building capacity for future. Innovations are the need of the day and oral vaccines for SARS-CoV-2 if successful and approved through established regulatory processes, will be beneficial, as they will enable better vaccine compliance.”
Dr. Raman Gangakhedkar, Former Head, Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research
“If the vaccine will be found as effective, it will also be useful in strengthening mucosal immunity. The currently available vaccines protect us from development of severe COVID disease or death. But they lose efficacy while protecting against acquisition of COVID infection. This route of administration may develop a stronger mucosal immune response and enhance vaccine’s efficacy in preventing it’s acquisition. It will also add to ease administration and thus a rapid rollout. This is an exciting development. More so, it is indigenous!”
Dr. Rakesh Mishra, Former Director, Centre for Cellular and Molecular Biology
“Nasal or Oral Vaccines are more effective options for the current COVID-19 vaccination efforts, as they offer significant logistics convenience of not having to have injections and needles. Also, the speed of the vaccination, which is the key in controlling the pandemic, will be accelerated which will be extremely useful. There are examples of such vaccines in the past and, therefore, there is good possibility that we may have Oral Vaccination option for COVID-19. However, no human trial has begun yet and it will be several months before any option of this kind is available.”
Dr. Chandrakant Lahariya, Public Health and Policy Expert
“This is an important development. Fighting pandemic require deploying all tools in science and technology. The one which we already have as well as new tools should be explored. Oral vaccines are available against various other diseases : poliovirus and Rotavirus. Therefore, in some sense the technology is known. However, every virus is different, therefore, we have to wait till process is completed. As far as SARS COV2 oral vaccine is concerned, we are at early stages, even the human trials have not started. I am optimistic but there is a long way to go“.
FAQs on Oral Vaccine in your minds
As answered by Dr. Prabuddha Kundu, Co-Founder and Managing Director, Premas Biotech
How many doses of oral vaccine for coronavirus will be needed ?
Ans: As of now, we have to conduct human trials to determine that, but in animals, a single dose demonstrated a significant immune response.
Till how much time one dose of oral vaccine for coronavirus will be effective ?
Ans: Effectiveness of one dose of oral vaccine for coronavirus needs to be determined.
Till when oral vaccine for coronavirus will come in market ?
Ans: If everything goes well, between 8-12 months oral vaccine for coronavirus will be made available.
Can people buy and use it on their own ?
Ans: That will be dependent on the individual regulatory authorities and Governments.
Oral vaccine capsules are new or there are other vaccine capsules too ?
Ans: Not that we know of for Corona Virus.
Oral polio vaccine has been very effective, what about oral coronavirus vaccine?
Ans: We will have to carry out the human trials and then the data will be available to understand the same.
Till now vaccines are not given to children, Can this be taken by children also ?
Ans: We will be applying to carry out trials in Children as well.
What is the cost of one dose of oral vaccine for coronavirus ?
Ans: While we have not determined that yet, it will be competitive as many of the other associated costs will not be there, like syringes, swabs, ultra-cold freezers, etc.
How to store the oral vaccine for coronavirus ?
Ans: We are attempting for room temperature storage.
What is the effectiveness of the oral vaccine for coronavirus as compared to the injectable vaccines available ?
Ans: In animal studies, all the three Ig classes were seen to be present at the various timelines, initially, IgM and then IgG and IgA.
Any risks associated with oral vaccine for coronavirus ?
Ans: We don’t see any risks attached with the oral formulation yet, but studies are still on going, and more data is being analyzed.
How difficult or easy it is to develop oral vaccine as compared to injectable vaccine?
Ans : The oral vaccines have been a need in the market, but have been difficult to achieve due to multiple factors. With this oral vaccine for SARS CoV-2, we wish to change that process.
What are these oral vaccines made up of?
Ans: These are soft gel capsules, which contain the Active Pharmaceutical Ingredients (API) and certain proprietary excipients. Proprietary ingredients consisting of excipient formulations include fragrances, flavours, colouring ingredients, trans-dermal patch adhesives and printing inks.
Briefly explain the process of developing oral vaccine for coronavirus ?
Ans: The Triple antigen virus-like particles (VLP) are dried as a powder and then formulated as a capsule. Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material.
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Note : This story was published in CSIR-NISCAIR’s prestigious magazine ‘ Science Reporter’ in June 2021.
If you are given a choice for vaccination –
You want to have the vaccine injected in your body with a syringe?
You want to get vaccinated with some nasal spray?
You want to swallow the vaccine with a few sips of water?
What will you choose? Many of us will straightaway choose the third or second option.
But wait. Vaccines are not like a simple medicine. Rather they are like an armour for our internal body to be protected from deadly viruses. So, its impact on our body should be the most important consideration while making a choice. A key vaccine should hamper multiplication and spread of virus. Till now no available vaccine controls virus infection the way it is supposed to be.
For the deadly coronavirus forcing us to lockdowns, curfews, masks and sanitizers all over again, oral vaccines are the new challenge. The journey has just begun… Scientists are on their job 24*7… and as per experts it will take almost an year or so for the oral vaccines to reach us, and we have hopes in our minds and souls. This hope has been ignited by a few players in the new drug delivery system arena.
Oral Vaccine Capsule
Latest to mention is an effort made by Oravax Medical, a joint venture of Gurugram-based biotechnology firm Premas Biotech and Oramed Pharmaceuticals, a company headquartered in Jerusalem… The process of oral vaccine development is in preliminary stage… Premas Biotech has a full fledged faculty consisting of scores of scientists specialising in different streams… Whenever a vaccine is developed, it goes through different phases… Like any other vaccine trial, Oral Vaccines are also first tested on animals like mice, rabbits or monkeys… The human trial is done at final stages and is subject to very stringent ethical norms, and medical regulations. Here, good news is that this Oral COVID-19 Vaccine ‘Oravax’ candidate produced antibodies after a single dose in pilot animal studies. Clinical trials will begin soon.
How Oral Vaccine Capsule is made?
These oral capsules are soft gel capsules, and they are manufactured in a specialized set up. They cannot be manufactured in the lab, but in a special machine that combines the materials and encloses them in a soft gel capsule.
How the oral vaccines Capsule work in our body?
Oral vaccines or any vaccine for it to be functional, has to perform its role, i.e. promote a robust immune response, and that immune response is protective. Oral vaccines as a method of delivery has not been so successful except for oral polio vaccine. So, the nature of the problem is to be able to avoid the acid of the stomach and the proteases in the small intestine. The small intestine or the gut in humans has its own set of immune cells and offers protection and immunity. For this we are in a wait and watch situation.
Intranasal Vaccine
Another oral vaccine in clinical trials now is the intranasal vaccine. To protect ourselves from the deadly coronavirus, the whole world relies on wearing masks… Reason being the virus enter the body through our nasal cavity and mouth… So, nasal tract is the most crucial area of attack by coronavirus. So, an intranasal vaccine is given through the nose, and it delivers the dose directly to the respiratory pathway, much like a nasal spray. Bharat Biotech is in licensing agreement with Washington University School of Medicine in St. Louis for a novel chimp- adenovirus, single dose intranasal vaccine for COVID-19. It is the first intranasal vaccine for COVID-19 and is already undergoing clinical trials. Thus nasal sprays are a ray of hope for effective vaccine.
How Intranasal Vaccine works ?
This is important to understand that immune responses at the site of infection i.e. in the nasal mucosa is essential for blocking both infection and transmission of COVID-19… And the Intranasal Vaccine is believed to do this efficiently by stimulating a broad immune response. When it is given through the nose, it gets absorbed in the mucus membrane, present in the upper throat where the absorption is much faster… It helps develop an immune response in the nose and develop antibodies… All these help not only prevent the infection but also killing the virus at the entry point and not allowing to hamper any of our body system… The intranasal vaccine requires only a single dose of 0.1 ml, using a spray in each of the nostrils…
Animal trials for Intranasal Vaccine
The trials in mice, Hamsters and Rhesus Macaques with single dose of intranasal vaccine conferred protection against SARS CoV2… Observations of animal trails showed clear lower and upper airways of respiratory tract from virus… The nasal route is an excellent way for vaccination as it is the entry point for the virus… It blocks the disease carrier and stops transmission of infection then and there… In India, the human stage trials for nasal vaccines have begun. Also, the results observed till now can vary for humans and overall. So, we need to wait for the final conclusions…
Intranasal vaccine VS Capsule vaccine : Which is more effective ?
Because of better compliance both the intranasal and oral immunization routes are attractive. Nasal immunization leads to induction of immune responses in the local nasal, adjacent oral and the distant mucosal sites. It induces a stronger mucosal response that can protect against the infection at the mucosal surfaces. Whereas oral immunization generates immune response in the gut. The mechanism of antigen processing and presentation by antigen presenting cells and the process of antibody generation, may not be very different between nasal and oral immunization. Importantly, responses in oral immunization are also good like in nasal immunization but they may not be as effective as nasal immunization when it comes to protection in the local nasal sites or respiratory tract.
We always talk about effectiveness of a vaccine, so let’s also explore how to make vaccine (Injectable/Oral-Intranasal or Capsule) effective on deadly virus? Nimesh Gupta adds – “To make an effective vaccine we should know where to hit on the virus that could restrict virus entry into the cells and its dissemination. Once we know the target of the virus, then we should know what kind and magnitude of immune response is required to confer a long-lasting protective immunity against this identified target. Next goal will be to achieve similar immune responses using a vaccine formulation. This is how a rational and effective vaccine could be developed against the complex virus”.
Benefits of Oral Vaccine
Oral vaccines
Challenges for Oral Vaccine
Unanswered questions :
No doubt oral vaccine in either way is the most patient friendly route, but there are unanswered questions. For any Vaccine, its efficacy is the most serious concern. It is believed that Oral vaccines, whether living or non-living, viral or bacterial, elicit diminished immune responses or have lower efficacy. And as our experts clearly indicate it is too early to come to conclusions. But, we know science has taken a leap. What was not possible a few years back is possible now, continues to develop in future and will remain forever.
FAQs on Oral Vaccine in your minds
As answered by Dr. Prabuddha Kundu, Co-Founder and Managing Director, Premas Biotech
How many doses of oral vaccine for coronavirus will be needed ?
Ans: As of now, we have to conduct human trials to determine that, but in animals, a single dose demonstrated a significant immune response.
Till how much time one dose of oral vaccine for coronavirus will be effective ?
Ans: Effectiveness of one dose of oral vaccine for coronavirus needs to be determined.
Till when oral vaccine for coronavirus will come in market ?
Ans: If everything goes well, between 8-12 months oral vaccine for coronavirus will be made available.
Can people buy and use it on their own ?
Ans: That will be dependent on the individual regulatory authorities and Governments.
Oral vaccine capsules are new or there are other vaccine capsules too ?
Ans: Not that we know of for Corona Virus.
Oral polio vaccine has been very effective, what about oral coronavirus vaccine?
Ans: We will have to carry out the human trials and then the data will be available to understand the same.
Till now vaccines are not given to children, Can this be taken by children also ?
Ans: We will be applying to carry out trials in Children as well.
What is the cost of one dose of oral vaccine for coronavirus ?
Ans: While we have not determined that yet, it will be competitive as many of the other associated costs will not be there, like syringes, swabs, ultra-cold freezers, etc.
How to store the oral vaccine for coronavirus ?
Ans: We are attempting for room temperature storage.
What is the effectiveness of the oral vaccine for coronavirus as compared to the injectable vaccines available ?
Ans: In animal studies, all the three Ig classes were seen to be present at the various timelines, initially, IgM and then IgG and IgA.
Any risks associated with oral vaccine for coronavirus ?
Ans: We don’t see any risks attached with the oral formulation yet, but studies are still on going, and more data is being analyzed.
How difficult or easy it is to develop oral vaccine as compared to injectable vaccine?
Ans : The oral vaccines have been a need in the market, but have been difficult to achieve due to multiple factors. With this oral vaccine for SARS CoV-2, we wish to change that process.
What are these oral vaccines made up of?
Ans: These are soft gel capsules, which contain the Active Pharmaceutical Ingredients (API) and certain proprietary excipients. Proprietary ingredients consisting of excipient formulations include fragrances, flavours, colouring ingredients, trans-dermal patch adhesives and printing inks.
Briefly explain the process of developing oral vaccine for coronavirus ?
Ans: The Triple antigen virus-like particles (VLP) are dried as a powder and then formulated as a capsule. Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material.
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