By Ritika Sakhuja

New Delhi: India has taken another huge leap in its fight against the COVID-19 pandemic with the introduction of iNCOVACC, a novel adenovirus vectored intranasal vaccine. Developed by Bharat Biotech using the licensed technology of ChAd-SARS-CoV-2-S from Washington University School of Medicine, iNCOVACC recently received Central Drugs Standard Control Organization’s (CDSCO) approval as a booster dose for adults across India. Additionally, Dr Mansukh Mandaviya, Union Health Minister, relayed that the National Technical Advisory Group on Immunisation (NTAGI) has also recommended iNCOVACC against COVID-19 as a booster dose for adults.

With the surge of coronavirus infections in China and the US, COVID-19 is rapidly expanding with new mutations occurring regularly, imposing the threat of morbidity, mortality, and socioeconomic disturbances, raising an alarm for developing herd immunity. Highlighting the need for COVID-19 vaccines as a global health priority, Dr Eric Feigl-Ding, Chief, COVID Task Force, New England Complex Systems Institute, Co-Founder, World Health Network and Chief Health Economist, Microclinic International said, “The need for different vaccine approaches to COVID-19 has become critically apparent with the continued emergence of variants to the SARS-CoV-2 virus.”

Experts suggest that iNCOVACC will be a game changer for the pharmaceutical industry and humanity’s fight against the COVID pandemic, even though not a lot of data has been disclosed publicly about the efficacy of iNCOVACC, unlike other COVID vaccines before it.

To understand the mechanism behind the functioning and administration of iNCOVACC and to motivate the masses to do their part in establishing collective immunity and furthering India’s pharmaceutical efforts by receiving the intranasal booster dose, ETHealthworld spoke to experts about the efficacy of Bharat Biotech’s vaccine.

Mechanism behind iNCOVACC: Administration and Halting Transmission

The nasal vaccine is a recombinant replication-deficient adenovirus vectored vaccine with a pre-fusion stabilized spike protein, as announced by Bharat Biotech.

As per a study by the Washington University school of medicine, a single-dose immunisation of rhesus monkeys with their ChAd-SARS-CoV-2-S via an intranasal route induced neutralising antibodies and T cell responses against SARS-CoV-2, in both the upper and lower respiratory tracts. Combining ChAd-SARS-CoV-2-S with the stabilised spike protein from SARS-CoV-2, Bharat Biotech created BBV154, which is the clinical codename for iNCOVACC.

Informing about the specificities of their intranasal vaccine, Bharat Biotech shared that iNCOVACC allows for a needle-free and painless experience as it has been formulated to be delivered as drops through the nose. “iNCOVACC is the first vaccine in the world to be approved for primary two-dose schedules and for booster doses. It is also the first nasal vaccine in the world to be administered as drops. iNCOVACC was specifically designed and formulated as nasal drops to ease administration,” said Bharat Biotech.

Since the vaccine is delivered via the nose, right where the virus enters the body, it has the potential to block infection and break the cycle of transmission, as well as prevent lung damage.

Explaining the probable efficacy of the intranasal route of administration, Dr Charu Goel Sachdeva, HOD and Consultant, Internal Medicine, HCMCT Manipal Hospitals said, “This vaccine has a huge advantage because it triggers a robust immune response at the nasal mucosa, the first place where viral transmission or viral infection can occur, leading to the production of neutralising IgG, IgA, and T-cell lymphocytes that can attack the virus and prevent even mild infection, hence preventing the spread of the infection. The nasal route has excellent potential for vaccination due to the organised immune systems of the nasal mucosa. This deterrent in the transmission is very important since it can reduce the spread of the virus and ultimately the chances of mutation in the virus.”

Intranasal Vaccine vs Intramuscular Vaccine

One upper hand that intranasal vaccines have over intramuscular vaccines is the ease of administration. With the introduction of iNCOVACC, Bharat Biotech promises that the intranasal vaccine could catapult the vaccination rates in India, by removing the hesitancy towards injections and the need for the expertise of the health worker administering the dose.

Highlighting the convenience offered by intranasal vaccines, Dr Suneetha Nareddy, Senior Consultant Infectious Diseases, Apollo Hospitals said, “There are several intranasal or inhalable vaccines that are in clinical development across the globe. There are 12 that we know of. China has two, one of which is CASINOS. Russia has SPUTNIK. Iran has a mucosal vaccine too. Primarily the reason why everyone is looking at the intranasal method of vaccines is the ease of administration. You don’t have to worry about syringes or needles, you can administer in mass numbers in the hope that you will get local immunity.”

Compared to injectable vaccines, nasal vaccines promise to induce protective immunity that could prevent or limit infection and also curb transmission of the virus because they enable immune defences right at the part of the body where the virus is most likely to enter. This could prove additionally beneficial for people who can’t get vaccinated or who are still at risk of severe illness despite vaccination, and the best way to protect them is to stop the virus from circulating.

Additionally, the iNCOVACC is designed in such a way that it is relatively quick and easy to update when new variants emerge, simply by switching out the current spike protein with one from a new variant.

However, Dr Sachdeva suggests that the intranasal vaccine is not here to replace the intramuscular vaccines. Instead, it will add to our arsenal allowing India to respond more effectively to the surge in COVID-19 mutations. “We are not pitching the nasal vaccine against injectable vaccines. Considering the spread of COVID-19 infection, the more vaccines we have the better it is right now. It is not that the previous intramuscular vaccines have not been effective. But intranasal vaccines can be given to the masses easily which can be an essential motivating factor for developing mass immunity,” she said.

Jury still out on Bharat Biotech’s iNCOVACC

After the studies in 2020 and 2021 led by the University of Washington demonstrated that the vaccine is effective in mice and non-human primates, Bharat Biotech launched two clinical trials of the nasal vaccine in India – a phase three trial involving about 3,100 previously unvaccinated people who received two doses of the nasal vaccine, and a booster trial with about 875 people who received a single dose of the nasal vaccine after two doses of another COVID-19 vaccine. These trials indicated that the vaccine is safe and effective at eliciting a strong immune response in people when used either as a primary vaccine or as a booster.

However, generally, when any pharmaceutical product is developed, the data surrounding its development and the results of clinical trials are put up for peer review so other scientists can vet the data. So far, this has not been the case with iNCOVACC.

“Currently, there are a lot of questions surrounding iNCOVACC for which we don’t have the answers. For this nasal vaccine, studies were conducted in animals where it was noticed that protection against SARS-CoV-2 lasted for several months. But as of now, we don’t know for how long this IgA response will be. In phase three of clinical trials, we know that immunogenesis occurred, but we don’t know the efficacy of whether it will prevent infections. Another question mark is whether this vaccine is going to be as effective against the omicron strain which is prevalent currently since the vaccine is manufactured using spike protein from the COVID strain that first originated in Wuhan. So there are a lot of things that we still don’t know,” said Dr Nareddy.

iNCOVACC’s indication, dosage, and cost

iNCOVACC has been indicated for anyone over the age of 18 who has received two doses of Covaxin or Covishield in the past. It will be used as a heterologous booster dose and will be available first in private hospitals and health centres, through the COWIN app from the fourth week of January.

Bharat Biotech told ETHealthworld, “Do note that the nasal vaccine is suggested as a first booster. It cannot be administered if someone has already taken a booster shot. The COWIN app will not allow users to book a fourth vaccine shot.” Government officials have stated that iNCOVACC will also be included in the vaccination program soon.”

“iNCOVACC will be given in two doses taken within an interval of four weeks from the first dose. The intranasal vaccine will be delivered as four drops in each nostril, a total of eight drops. The vaccine will be administered through a slow drip process of delivery rather than a single shot or spray to avoid excess liquids that run down the nostrils post-nasal drip in certain cases. The objective is for the entire antigenic payload to be fully absorbed and not wasted,” the company stated.

The biotechnology company said that iNCOVACC has been competitively priced for both government and private markets, costing 800 rupees for private markets and 325 rupees at government centres.

Encouraging the masses to join in on this fight against COVID, Dr Sachdeva recommended, “Going by the need of the hour, especially now with the huge number of cases in China and US and other countries, it becomes very important that people get their booster doses quickly. A good number of people have already gotten their second dose but a lot of people still haven’t taken the booster dose.”

Vouching for the intranasal vaccine, Dr Nareddy said, “The main thing is that iNCOVACC is convenient, can be implemented on a large scale, compliance will be better, and it may cover the other emerging strains as well. This vaccine has been studied as a primary vaccine also. Though the government has recommended it only as a booster, there were 3000 people where they studied it as a primary vaccine, so there is data supporting that even as a primary dose it will work.”

Currently, healthcare experts are of the opinion that the rollout of iNCOVACC is a remarkable step that will strengthen India’s position in the global pharmaceutical market and put the country miles ahead in its response to the COVID-19 pandemic. However, due to the lack of peer-reviewed data, experts suggest that the efficacy of iNCOVACC can be objectively measured only after the rollout of the vaccine happens among the masses, and thorough data is made available showcasing the immune response that is subsequently elicited after the administration of Bharat Biotech’s intranasal vaccine.