BEIJING (BLOOMBERG, AGENCE FRANCE-PRESSE, REUTERS) - China's recent approval of clinical trials of a Covid-19 vaccine administered by inhalation has cast the spotlight on alternative ways of delivery as the world continues to battle the pandemic.

Chinese company CanSino Biologics said in a filing on the Hong Kong stock exchange on March 23 that the inhalation vaccine candidate is jointly developed with the Beijing Institute of Biotechnology.

CanSino said its application for human testing received the green light from the Chinese authorities on March 22. But the company warned that the vaccine's safety and efficacy are subject to confirmation in trials.

CanSino had developed an injection-based, single-dose Covid-19 vaccine that is being used in China. It has also been approved for use in Pakistan, Mexico and Hungary.

Its inhalation vaccine candidate is no different in terms of virus species, cell banks, production technology or preparation formula from the injection-based Covid-19 vaccine, said Chinese state-owned newspaper Global Times. However, it has an atomisation inhalation device.

This device enables the vaccine to be atomised into tiny particles and then inhaled into the respiratory tract and lungs to stimulate an immune response in the mucous membranes, a Beijing-based immunology expert, who declined to be named, told the Global Times.

One important goal of an inhaled vaccine is to prevent the pathogen from growing in the nose, a point from which it can spread to the rest of the body, and to other people.

Research by scientists at Imperial College London, published in the journal Science last October, showed that a strong mucosal immune response is vital for staving off respiratory infections.

Professor Jiang Chunlai from Jilin University's School of Life Sciences told the Global Times: "We have seen intranasal vaccines against influenza in China. But there have been limited clinical studies on inhaled (Covid-19) vaccines."

Prof Jiang said further clinical trials are needed to determine the dosage, and inhalation is also not suitable for all types of vaccines.

CanSino's inhalation vaccine candidate is not the first that uses an alternative delivery method.

Last November, an experimental dual vaccine for both influenza and Covid-19 delivered via a nasal spray entered the stage of human studies in Hong Kong.

The clinical trial was to enrol about 100 adults, said Professor Yuen Kwok Yung, chairman of infectious diseases at The University of Hong Kong's department of microbiology.

The candidate vaccine is similar to a nasal spray flu immunisation already on the market that is designed to start working where respiratory viruses typically enter the body - the nose.

The joint study by researchers from the University of Hong Kong, Xiamen University, and vaccine maker Beijing Wantai Biological Pharmacy started last October.

The clinical trial will seek to demonstrate the vaccine's safety as well as the optimal dosage.

Inhaled-vaccine makers are counting on some of the unique features of the nose, throat and lungs that are lined with mucosa. This tissue contains high levels of immune proteins called IgA that give better protection against respiratory viruses. Activating these immune weapons can protect areas deeper in the lungs where the virus does the most damage.

In a study of mice last August, infectious disease specialist Michael Diamond and his team from Washington University in St Louis found that delivering an experimental vaccine via the nose created a strong immune response throughout the body; the approach was especially effective in the nose and respiratory tract, preventing infection from taking hold.

Vaccines that are sprayed into the nose or inhaled may hold other practical benefits. They do not require needles, and would be useful for children or those who fear needles. They may not need to be stored and shipped at low temperatures, and can reduce the need for health workers to administer them.

"The vaccines that can be delivered to generate (local immunity) will have some advantages over vaccines that are delivered systemically," said immunologist Frances Lund from the University of Alabama who is working with biotech firm Altimmune on a nasal vaccine currently being evaluated in a phase one clinical trial.

Scientists at the University of Oxford and Imperial College London are studying inhalation vaccines, which would be delivered through a mouthpiece in an aerosol, similar to some asthma therapies. Data from the trials could come by the second quarter of this year.

Oxford University is also launching a separate study on the immune response of a nasal administration of its vaccine developed with AstraZeneca, with 30 health volunteers aged 18 to 40 for the initial trial.

Despite the advantages, the delivery device in an inhalation vaccine is more complex than a syringe, said Dr Nick Jackson, head of programmes and technology at the Coalition for Epidemic Preparedness Innovations (Cepi). There are also questions on how long protection from such vaccines would last.

Still, researchers said targeting the airways may pay off down the road. The Oslo-based Cepi has provided funding to the Hong Kong trial, Dr Jackson said, and is open to further investments in candidates that employ unconventional methods, as part of an effort to supply billions of doses to every corner of the world.

Taking vaccines via nose or inhaling

Advantages:

• Such vaccines do not require needles, and would be useful for children or those who fear needles.

• May not need to be stored and shipped at low temperatures.

• Reduce the need for health workers to administer them as no needles are used.

• Potentially more effective at blocking the pathogen immediately when the virus is inhaled or comes into contact with the nose.

Disadvantages:

• Delivery device is more complex than a syringe.

• Theoretical benefits are uncertain without efficacy trials.

• Some who receive the vaccine through the nose may sneeze immediately after, causing some of the vaccine to be expelled, thus affecting dosing.