The novel coronavirus, SARS-CoV-2, has led to an unprecedented international health crisis and is continuing its spread across the world, with more than 218 million confirmed cases of COVID-19, including more than 4.5 million deaths, reported to the WHO as of 3 September 2021. (1)

More than one year into the pandemic, the vaccines for the COVID-19 have been developed in record time as a potentially effective prophylactic strategy.  However, despite the amazing progress, there is a strong demand for more options that are more accessible, easier to store, and more effective vaccines. In developing countries, the critical issue is a lack of access to vaccines,  or no infrastructure and personnel to deliver the injections en masse. In developed countries, the key issue is the lack of willingness to get vaccinated, an aversion to needles, and a lack of trust for the vaccines and injections in general. To date, with 40.4 % of the world population fully vaccinated, more options are sorely needed. (2)

The good news is that an oral virus-like particle (VLP) COVID-19 vaccine by Oravax , an Israeli pharmaceutical Oramed is being tested in preclinical studies against COVID-19 variants including the Delta variant. Study data demonstrated that the oral COVID-19 vaccine promoted both systemic immunity through Immunoglobulin G (IgG), the most common antibody in blood and bodily fluids that protects against viral infections, and Immunoglobulin A (IgA), which protects the respiratory and gastrointestinal tracts against infection. (3) If you want to get more information on COVID-19 and pharma, Pharmasouce would be your best choice.

Based on existing technologies, the scientists have designed synthetic particles that mimic three key structures of the coronavirus pathogen: the spike protein, the envelope protein, and the membrane protein, that includes more elements than the currently approved vaccines, which should enable the pill to better protect against current and future variants of the COVID-19 virus. As we know that the current vaccines in circulation focus on the spike protein, so adding more of these can help boost the overall effectiveness of vaccines.

How will the oral vaccine work? A challenge is the difficulty ensuring that the vaccine survives the acidic environment, Oramed believes they can create a capsule that is strong enough to withstand the stomach acid as necessary since the company has previously had experience working with protective coating for insulin with Avram Hershko, a Nobel-winning biochemist, showing that it is possible to create capsules.(4)  Oramed hopes to use the same technology for the oral VLP COVID-19 vaccine development.

Oravax claims oral COVID-19 vaccine is  safe, efficacious, and well-tolerated at normal to high doses, and generates high titers of neutralizing antibodies, which can potentially be more effective against current and future variants of the COVID-19 virus. The VLP vaccine can also be used both as a standalone vaccine and a booster for people who have been previously vaccinated for COVID-19.(3)

The oral VLP COVID-19 vaccine is poised to begin clinical trials during the second quarter of 2021, first in Israel, then in additional clinical sites  in multiple countries, including the United States, Europe, and Mexico. The clinical study protocol has been approved by the Institutional Review Board (IRB) at Ichilov Hospital in Tel Aviv Sourasky Medical Center, Israel's leading multidisciplinary healthcare institution, and is now pending approval from the Israeli Ministry of Health. GMP manufacturing for the oral vaccine is underway.  As with other vaccines, the trials will move in phases to show success, safety, and efficacy. If the trials prove successful, Oravax hopes to seek emergency approval in countries that are facing vaccine deficits, in particular, developing countries. (5)

Oral vaccines come with a variety of advantages. They can be taken at home and reduce the need for medical professionals who have to administer them, an especially big concern in developing countries. In developed countries, oral vaccines offer an advantage for people who fear needles. Oral vaccines cut out the need for freezing equipment for transportation and storage and eliminates bio-hazardous waste problem. Take together, the oral vaccines may offer relative advantages concerning safety, efficacy, compliance, ease of manufacturing and administration with  fewer side effects. (4)

Currently, a number of research groups throughout the world are now also working intensively to create oral vaccines against COVID-19 besides Oravax. With a similar approach, another Israeli team from the MIGAL Galilee Research Institute’s biotechnology group began development on what they hoped would be an oral coronavirus vaccine in February 2020. The scientists said they were primed to develop their vaccine within a few months. (6)

Vaxart,  a US-based clinical-stage biotechnology company has recently been cleared by the U.S. Food and Drug Administration (FDA) for its drug application for an oral recombinant COVID-19 vaccine tablet, that has moved to the Phase-I clinical trial (NCT04563702).(7) It is an S-only vaccine based on an orally administered adenoviral-vector-based vaccine (VXA-COV2-1) expressing a SARS-CoV-2 antigen and dsRNA adjuvant that is expected to produce higher serum  antibodies. (8)

Another oral vaccine candidate under development by a UK-based company iosBio (previously known as Stabilitech) is OraPro-COVID-19TM.(9) It uses a non-replicating viral-vector that expresses the ‘S’ protein and is used as a thermally stable capsulated form, which meant there is no need of refrigeration which could be a major problem with many other vaccine candidates that need a lower temperature for storage and deployment, especially in developing countries.

In addition, the Chan Soon-Shiong Research Institute in El Segundo, California is also testing oral capsules as an alternative and, perhaps, a more effective alternative to COVID vaccines. The researchers point out another advantage, the possibility of storing the pills at room temperature. Currently, the oral vaccine is under testing with healthy volunteers. (10)

More recently, Pfizer is also getting into the game of oral solutions for COVID-19. It is currently testing an oral medication for COVID in various clinics, including the Austin Regional Clinic, to see whether the oral medication being used can reduce symptoms for high-risk and low-risk individuals. While not a vaccination, it is meant to see whether the oral solution can reduce symptoms and prevent the onset of COVID-19 symptoms among household members. (11)

There is another approach,  West Virginia University scientists are working on a nasal mist as a vaccine, similar to a flu vaccine that can also be offered nasally. Administering vaccines nasally could encourage the development of strong antibody responses. (12) This is a type of research undertaken alongside oral vaccines and might serve as a complement to the oral solutions.

Oral solutions might be combined with nasal solutions for greater efficacy. A study from University of Tokyo researchers has found that oral bacteria-combined intranasal vaccine can protect individuals from COVID-19. Moreover, data showed that oral bacteria-combined intranasal vaccine protects from influenza virus and SARS-CoV-2 infection. (13)

As of August 31, 2021, there have been  297 COVID-19 vaccine candidates in both clinical and pre-clinical development worldwide,(14) only 8 studies are for oral COVID-19 vaccine. (15)  Based on current progress, the COVID-19 oral or nasal vaccine is closer to being a reality, offering more vaccination opportunities for developing and developed countries, but it still needs to undergo clinical trials and receive all the proper approvals. We urgently expect a safe and effective oral COVID-19 vaccine to the market as early as possible.

References

1    https://covid19.who.int

2    https://ourworldindata.org/covid-vaccinations

3   https://www.ora-vax.com

4   Ahmed, I. (2021) https://medicalxpress.com/news/2021-08-israeli-company-oral-covid-vaccine.html

5   Hart, R. (2021) https://www.forbes.com/sites/roberthart/2021/07/22/oral-covid-vaccine-set-to-begin-trials-in-israel/?sh=7a9a31091ba5

6   https://www.migal.org.il/en/coronavirus-vaccine-project

7 https://www.clinicaltrials.gov/ct2/show/NCT04563702?term=NCT04563702&cond=NCT04563702&draw=2&rank=1

8   Vaxart. (2021) https://www.prnewswire.com/news-releases/fda-clears-vaxarts-ind-application-for-s-only-oral-tablet-covid-19-vaccine-candidate-301345771.html

9   https://iosbio.com_

10 CBS News. (2021) https://www.cbsnews.com/news/covid-19-vaccine-oral-testing-los-angeles/

11 Ashbrook, M. (2021) https://www.kvue.com/article/news/health/coronavirus/austin-regional-clinic-pfizer-covid-oral-medication-treatment-study/269-f3f9e400-a4a0-44aa-ac8d-2839e47fda21

12 Lynch, D. (2021) https://www.wtrf.com/news/health/coronavirus/wvu-scientists-developing-nasal-mist-vaccine/

13 Basu, M. (2021) https://www.msn.com/en-in/health/medical/how-nasal-bacteria-could-hold-key-to-improving-intranasal-covid-vaccines/ar-AANqVYU

14 https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

15 https://www.clinicaltrials.gov/ct2/results?cond=oral+COVID-19+vaccine+&term=oral+COVID-19+vaccine+&cntry=&state=&city=&dist=).

About the Author:

Lin Zhang, M.D., senior director of a health care industry company in the United States. With the experience in clinical medicine, biotechnology, health industry and other fields, he is responsible for the research and development of plant medicine, functional food and health products. He was a clinician and worked for the National Cancer Institute, FDA and the National Cancer Center of Japan for many years.