A safe and effective vaccine against COVID-19 is eagerly awaited as the answer to a pandemic, which is raging across countries. Work on a coronavirus vaccine began as early as 10^th January. Since then, more than 190 trials of COVID-19 vaccine are underway worldwide. These trials are at various stages in the process of vaccine development. Different technology platforms, such as live attenuated virus and inactivated virus, viral vector, virus-like peptide, nucleic acid (DNA and RNA), recombinant protein, have been used. It’s a race against time and it is hoped that we won’t have to wait too long to see who reaches the finishing line first.

The frontrunner vaccine candidates are the Oxford-Astrazeneca vaccine, Sputnik V, Moderna, Johnson & Johnson (J&J).

The Oxford-AstraZeneca vaccine, ChAdOx1 (AZD1222), is undergoing phase 3 trials in many countries around the world. It is a vector vaccine and has used a nonreplicating chimpanzee adenovirus vector. The Serum Institute of India is conducting phase 3 trials of the Oxford vaccine as part of international trials in India. Results are expected this month or early December.

The J&J vaccine, JNJ-78436735 (Ad.26.COV2.S), is a single dose vector vaccine and has used a variant of a human adenovirus Ad26. Biological E has collaborated with J&J for the technology transfer of their vaccine candidate and will conduct trials for this vaccine in India.

The phase 3 trials of both the Oxford-AstraZeneca vaccine and the J&J vaccine had been temporarily paused because of an unexplained illness in a participant. AstraZeneca has resumed its trials in the UK, Brazil and South Africa after safety reviews. The US FDA has also now given the go-ahead for the trial to restart in the US. J&J has also resumed trials in the US.

Russia was the first country to register its coronavirus vaccine, Sputnik V, for use as early as in August, although phase 3 clinical trials had not been done. This is a vector vaccine, but has been developed with two vectors (Ad26 and Ad5). The DCGI has approved phase 2/3 human clinical trials of Sputnik V in India to be conducted by Dr Reddy’s Lab.

Pfizer and BioNTech are co-developing a messenger RNA (mRNA) based 2-dose vaccine “BNT162b2”. Pfizer hopes to apply for emergency use authorization for its COVID-19 vaccine in the third week of November after safety data of its phase 3 trials in the US is available and reviewed. Combined phase 1 and phase 2 clinical trials of this vaccine have been started in Japan.

The “mRNA-1273” vaccine developed by Moderna in partnership with the National Institutes of Health (NIH) is also a leading player. Moderna is preparing for the global launch of their vaccine. Results of the phase 3 trials are expected this month.

So far, India has three vaccines in different stages. Of these, two are indigenous COVID-19 vaccines: Covaxin and ZyCov-D.

Covaxin (BBV152) by Bharat Biotech has been developed in collaboration with the Indian Council of Medical Research (ICMR)-National Institute of Virology (NIV). It is an inactivated virus vaccine. ZyCov-D is a DNA vaccine developed by Cadila Healthcare. Both these vaccines are undergoing phase 2 trials. Bharat Biotech has received regulatory approval to proceed with phase 3 clinical trials of its vaccine. More than 26,000 subjects have been recruited for the trials, which will be conducted in more than 25 centers across the country.

The third vaccine in the country is the Oxford-AstraZeneca vaccine. It has been given the name “Covishield”. The Serum Institute of India is working on it and has approval for phase 3 trials of this vaccine.

Together with ICMR, Serum Institute of India will also work on the development of a glycoprotein subunit nanoparticle adjuvanted vaccine developed by Novavax, an American vaccine development company.

Throat is a major site for the replication of COVID-19 virus resulting in high shedding of the virus, when the illness is still mild.¹ Therefore, it is easily transmissible.

Gargling removes the pharyngeal protease, which facilitates viral replication.² This reduces the viral load in the throat and also the amount of virus exhaled. ³ Among the various antiseptics available, povidone-iodine (PVP-I) has the broadest spectrum of antimicrobial activity; rapid and persistent effect, lack of resistance are its other desirable characteristics.⁴

PVP-I gargles has been shown to have ≥ 99.99% virucidal activity within 30 seconds against the SARS-CoV-2 virus in in vitro studies.⁵ A comparative study from Malaysia demonstrated 100% viral clearance as early as 4 days after the intervention following PVP-I gargling. In the same study, viral clearance was 80% with essential oils gargling and 20% with tap water gargling. An individual who has COVID-19 is highly infectious even at the early stage of the infection; hence, early clearance of the virus is very important to reduce the transmission.⁶ Other studies have also shown virucidal activity of PVP-I against the virus in only 15 seconds. ^7,8

We do not know if and when a safe and effective COVID-19 vaccine will be available. The earliest a vaccine can be expected is by early to mid next year. But, then logistics have to be decided upon. Who will get the vaccine first? A roadmap for administration of vaccine to the people has to be developed. 

Till a vaccine or a specific treatment is available, preventive measures (masking, hand hygiene and physical distancing) are the only answer. These are the best ways to protect oneself from the infection. Gargling with an antiseptic such as PVP-I can be added to these measures to further augment the control of the spread of the infection.

References

1. Wölfel R, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 May;581(7809):465-9.
2. Kitamura T, et al. Can we prevent influenza-like illnesses by gargling? Intern Med. 2007;46(18):1623-4.
3. Herrera D, et al. Is the oral cavity relevant in SARS-CoV-2 pandemic? Clin Oral Investig. 2020;24(8):2925-30.
4. Lachapelle JM, et al. Antiseptics in the era of bacterial resistance: a focus on povidone iodine. Clin Pract. 2013;10:579-92.
5. Anderson DE, et al. Povidone-iodine demonstrates rapid in vitro virucidal activity against SARS-CoV-2, the virus causing COVID-19 disease. Infect Dis Ther. 2020:9(3):669-75.
6. Tsai C, et al. Possible beneficial role of throat gargling in the coronavirus disease pandemic. Public Health. 2020;185:45-6.
7. Bidra AS, et al. Rapid in-vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using povidone-iodine oral antiseptic rinse. J Prosthodont. 2020;29(6):529-33.
8. Mohamed NA, et al. Early viral clearance among covid-19 patients when gargling with povidone-iodine and essential oils – a clinical trial. MedRxiv. September 9, 2020.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA