nasal shots
An intranasal vaccine is more acceptable to parents of young children. A nasal vaccine could save on medical equipment, such as syringes, too, say experts. Image Credit: Gulf News/ Jay Hilotin

Highlights

  • There are at least 8 intranasal vaccines under development
  • A nasal shot can be “self-administered”, a do-it-yourself type of vaccine which can save time taken for vaccination
  • A nasal spray against COVID-19 targets the immunisation of the upper respiratory tract
  • This way, it prevent individuals from spreading the virus and developing infections in other organs of the body
  • Israel and New Zealand already gave interim approval for sale of the SaNOtize COVID-19 nasal spray, one report states

The next generation of COVID-19 vaccines may no longer need a syringe. A nasal spray offers a number of benefits over traditional approaches to vaccine administration, and is more preferred by parents for their children, according to researchers.

So a squirt in the nose — instead of a shot in the arm — could be a godsend for several reasons. For one, they would help ward off coronavirus and help beef up the approved regime of intramuscular vaccines, which are in short supply globally due to production shortfalls.

Currently the supply of COVID-19 vaccines is extremely limited, and the majority of doses are going to high-income nations that only account for 16% of the global population. Here’s the lowdown on nasal COVID shots and how they may change the game:

Q: What is nasal vaccine?

A nasal shot, formally called “intranasal” vaccine, is administered by squirting or spraying the solution into the nostrils instead of injecting it in the arm.

The idea is that, one gets infected through the nose. It’s very appealing, for that reason, to immunise directly in the nose, because then you will stimulate the immune system where you need it the most.

- Dr Bill Petri, infectious disease professor, University of Virginia

Q: How effective is it?

In animal models, such as chimps and rodents, several experimental nasal sprays were shown to work in effectively reducing COVID-19 “viral load”. In the SaNOtize human trial, the self-administered treatment showed an extremely high efficacy rate — up to 99% drop in “viral load” within 72 hours, according to a Reuters report.

This is an exciting development. This trial — fully randomised, double-blinded and placebo-controlled — involved 7,000 participants, a decent and statistically significant number for a Phase 2 test.

Evidence is building up to bolster the utility of nasal vaccines in stimulating a broad immunte response against the coronavirus. For example, experts from Lancaster University in England and Texas Biomedical Research Institute in San Antonio,  reported that their nasal spray vaccine against COVID-19 shows “promise” — kicking up antibody and T-cell responses that were strong enough to suppress SARS-CoV-2. The vaccine also reduced lung damage, inflammation and disease severity in mice.

“Administering this vaccine through a nasal spray completely protected the animals from shedding the virus which causes transmission of the virus. This means the immunisation of the upper respiratory tract through a nasal spray can prevent individuals from spreading the virus and developing infections elsewhere in the body,” said study author Muhammad Munir, a Lancaster University virologist.

Q: What is the efficacy needed for nasal vaccines against COVID?

They must have efficacy of at least 50% — the benchmark set by the World Health Organisation for the vaccine to be endorsed by the global health body.

Q: Who are working on nasal vaccines?

The World Health Organisation's (WHO) vaccine “landscape” shows several companies are in the running for making billions of doses of nasal-spray vaccines against COVID-19. At least eight research groups are working on such projects, based on the WHO list updated as of April 30, 2021.

nasal shots
Image Credit: Gulf News/ Jay Hilotin

Q: Is there a nasal vaccine in use today?

Yes. It’s one of the miracles of biotech. Administering a vaccine via the nasal route has already been proven effective against the flu virus, a seasonal disease that kills hundreds of thousands of people each year.

It’s been hypothesised that the nasal route would also work against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).

Since year, animal studies had already borne this out. For example, in a study published in Cell on August 19, 2020, scientists at the Washington University School of Medicine demonstrated their experimental intranasal vaccine as having the ability to kick up immune response in the mucosa — which prevents COVID-19 infection in chimpanzees.

In that experiment, using animal models, intranasal vaccine delivery generated robust mucosal B- and T-cell responses using the ChAd-SARS-CoV-2 vector. It also found to prevent upper and lower respiratory tract infection, according to the study. The WU nasal spray, which uses adenoviral vaccines encoding stabilised S-induce neutralising antibodies, makes it difficult for the virus to attach to human cells and, when used daily, it is able to block transmission of the virus.

Q: What are the other applications of nasal vaccines?

Besides respiratory infections, the nasal route has been used to deliver vaccines even for sexually transmitted infections, according to the US National Institutes of Health.

The rationale for targeting mucosal tissue in the genital tracts can be attributed to the mucosal immune system.

Mucosa, mucosal immunology
The mucosa is the moist, inner lining of some organs and body cavities (such as the nose, mouth, lungs, and stomach). Glands in the mucosa make mucus (a thick, slippery fluid).

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract and the respiratory system, i.e., surfaces that are in contact with the external environment.

Source: NCBI/National Institutes of Health

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract and the respiratory system, i.e., surfaces that are in contact with the external environment.

Q: How many intranasal vaccines are being tested against COVID-19?

There are at least eight intranasal vaccines being developed — in the UK, Canada, the US, China, India and Peru — with some progressing to human testing.

nasal shots
Image Credit: Gulf News/ Jay Hilotin

Q: What’s the advantage of a nasal COVID-19 vaccine?

A nasal COVID vaccine, if approved, is seen to offer the following advantages?

  • No more need for syringes;
  • A low-cost alternative for the developing world;
  • Ability to scale up using the existing global infrastructure currently in use for influenza virus vaccines;
  • Offers the most economical vaccine supply worldwide;
  • Simple administration (self-administration, DIY)

Dr Mohammed Rohaim forms part of a team developing a nasal spray against COVID at the the Lancaster University. He said: “Scalability and economical production make this vaccine candidate suitable for low- and middle-income countries.”

Lancaster University’s Dr Munir has world-leading experience in the “reverse genetics” of the Newcastle disease virus (NDV) — a virus safe for humans but that can be harnessed as vector against coronavirus. “This method has provided us with a way to insert the genes of other viruses into the NDV — to make a vaccine against literally any pathogen,” Dr Munir told the university’s newsletter.

Q: What is the status of India’s Bharat Biotech nasal vaccine?

On January 8, 2021, it was reported that Bharat Biotech was seeking the Drugs Controller General of India (DCGI) nod to conduct Phase 1 trials of nasal COVID-19 vaccine.

Documentation for the Bharat Biotech nasal vaccine made available on clinicaltrials.gov (NCT number NCT04751682), run by the US National Institutes of Health, shows that the study kicked off on March 1, 2021, targeting trial participant ages 18 to 60. Primary completion date was expected on March 25, 2021. The full trial is being conducted in several hospitals in India, including AIIMS Patna, Apollo Hospitals Chennai, St. Theresa Hospital Hyderabad, Gillurkar Multispeciality Hospital Nagpur. It is expected to be completed by November 30, 2021.

If successful, Bharat Biotech could be one of the top-runnings in the mass-production of nasal spray vaccines that would help the world fight COVID-19 infection and transmission.

Vaccine trials, depending on budget and availability of volunteers, generally take time. But they can be accelerated with government support and the spirit of volunteerism.

Q: But would nasal vaccines actually work against COVID?

For COVID, the safety and efficacy profiles of intranasal vaccines are still under clinical trials. They would have to complete large-scale trials, the same way intramuscular vaccines were tested before getting emergency use authorisation (EUA) in most countries.

Q: Which research team is farthest along the nasal vaccine trial marathon?

The team that has reached the farthest on the clinical trial marathon so far — currently in Phase 2 out of the 3-phase trials — is SaNOtize of Canada, and University of Hong Kong (UHK) in partnership with Xiamen University and Beijing Wantai Biological Pharmacy of China.

Q: Are these nasal sprays designed for be self-administered?

The nitric oxide nasal spray (NONS) made by Vancouver-based biotech firm SaNOtize is designed as a do-it-yourself vaccine.

Q: How was the trial conducted? What were the initial results?

It was done through a randomised, double-blind, placebo-controlled Phase II trial. In March 15, it evaluated the first 79 confirmed cases of COVID-19.

In a trial on 7,000 patients, researchers stated those with a self-administered nasal spray application were found to have reduced SARS-CoV-2 log “viral load” by more than 95% in infected participants — within 24 hours of treatment, and by more than 99% in 72 hours.

Theclinical trials were conducted in Canada and most recently, the UK. SaNOtize announced the results of Phase II trials alongside Ashford and St Peter’s Hospitals NHS Foundation Trust and Berkshire and Surrey Pathology Services in the UK.

SaNOtize spray Phase 2 trial results
SaNOtize’s early treatment significantly decreased the level of SARS-CoV-2, including in patients with high viral loads infected by the concerning UK variant of COVID-19.

Patients treated with SaNOtize’s spray saw an average viral log reduction of 1.362 in the first 24 hours, corresponding to a decline of around 95%. Within 72 hours, the viral load plummeted by more than 99%.

Q: What are the implications of the SaNOtize nasal spray study?

It’s a dramatic reduction, if the results are verified. If approved, it would be a safe and powerful antiviral that could prevent the transmission of COVID-19, cut its duration — and reduce the severity of symptoms in those infected.

Q: What about adverse reactions?

No adverse events were recorded in the UK trial nor in earlier Canadian trials that saw over 7,000 patients testing the self-administered treatment.

“I expect this to be a major advance in the global battle against the devastating human impacts of the COVID-19 pandemic,” said consultant medical virologist and chief investigator of the NHS trial Dr Stephen Winchester.

Q: Revolutionary?

At present, outside of monoclonal antibodies, NONS is the only novel therapeutic treatment been proven to reduce SARS-CoV-2 viral load in humans, SaNOtize said.

The SaNOtize treatment kills the virus in the upper airways, preventing it from incubating and making its way to the lungs.

“This simple portable nasal spray could be highly effective in the treatment of COVID-19 and reducing onward transmission. Our trial included patients with a variant of concern and high viral loads yet still demonstrated significant reductions in the levels of SARS-CoV-2, which could be critical in supporting vaccines, preventing future outbreaks and safely reopening economies. Simply stated, I think this could be revolutionary,” said NHS’s Dr Winchester.

Q: Is SaNOtize nasal shot already approved?

The biotech firm said Israel and New Zealand have given interim approval for the sale of their Nitric Oxide Nasal Spray (NONS), according to a March 22, 2021 Reuters report quoting the company. This could not be independent verified as of publication time.

Q: Would a nasal vaccine be a game-changer?

It could, for reasons stated above, and again. below:

  • One, simplicity — the ability of people to self-administer the vaccine.
  • Two, appeal — it’s more appealing to parents with young children.

“There’s no need for needles,” Dr Bill Petri, an infectious disease professor at the University of Virginia. “We’re working on a device that you would actually spray into your nose, not similar to an inhaler, which you spray through your mouth, said in an interview with WTKR on February 16, 2021.

  • Three, scalability.

The world, especially poorer nations with no access to vaccines, need all the help they can get today. A Duke University study predicted that at the current rate of production of approved vaccines, the world's 92 poorest nations won’t have enough vaccines for even 60% of their populations until 2023 — meaning the pandemic could drag on for years.

Q: What’s the status of COVID-19 nasal vaccine clinical trials — and production?

There are many hurdles faced by the nasal vaccines: Complete all three phases of clinical trials. This entails the several thousand of volunteers. Funding would have to be secured for these trials.

Follow the “gold standard” of scientific investigations — double-blind, randomised and placebo controlled. After the trial is completed, typically in a few months, an initial data analysis “read-out” would have to be made. Subsequent read-outs are needed a few weeks later, to confirm initial numbers.

If the efficacy level is good, the vaccine developer must apply for authorisation with the drug regulators in different jurisdictions. But that also means, first and foremost, having the ability to mass produce and distribute them. This involves a different challenge altogether. But, given the global ramp in production and distribution, there's hope that things would get so much better if the right steps are taken.