Why the nasal vaccine may be the next step in the fight against COVID-19

The Ómicron variant of the coronavirus stood out for its high transmissibility compared to all previous ones. It was detected last November and produced explosive waves of COVID-19 in most countries, and it again generated spikes over the past two months even among people who were already vaccinated. For the future, today more and more dedication is being made to the development of nasal vaccines that could prevent the entry of coronavirus to the human organism.

While the vaccines already available are injected and protect people against serious illness, hospitalization and death if they get coronavirus, there are now scientists who are more directly aiming to prevent the infection from being acquired. They hope to achieve this by developing vaccines that are placed with a nasal spray. The idea they pursue is to block the possibility of the virus entering completely in healthy people.

“Nasal vaccines against COVID-19 may have benefits at this point in the pandemic. Among other advantages, one possibility is that they stop infections,” Dr. Guillermo Docena, a researcher at Conicet and the National University of La Plata, told Infobae. This scientist is leading the development of a type of nasal vaccine in Argentina, which is at the stage of pre-clinical studies.

With the nasal inoculant, it would be switched from injection into the arm to inhalation through the nose. A wall of immunity could be created just where viruses find their foothold and stop the spread of the virus. In this way, even minor infections by the Ómicron variant and its sublinages or by some other variant that could arise would be avoided.

In the global scientific community there is a debate about whether to continue with more booster doses in the coming months or whether to change the strategy in the type of vaccines that are applied. In March, the United States government presented the National COVID-19 Preparedness Plan last March, emphasizing the need to restart vaccines to adapt them to variants within 100 days of their appearance and to develop a universal vaccine. That is, a vaccine “that protects against COVID-19 and all its variants, as well as against future emerging coronavirus threats”.

Scientist Akiko Iwasaki, an immunologist at Yale University School of Medicine, in the United States, had said in early 2021 that she was thinking about her research on the nasal vaccine in preparation for the next pandemic. But Omicron put his plans forward to him.

“Seeing all these new variants that are much more transmissible and that render our vaccines useless for infection prevention, that's when we realized that we could have the opportunity to contribute something during this pandemic,” Iwasaki told The Washington Post.

Iwasaki has already developed a nasal spray consisting of the spike protein in a saline suspension. This strategy would not work as a first round of vaccination but could be powerful as a reinforcement. The technology was licensed to the company Xanadu Bio, in which Iwasaki is co-founder.

There are several projects to develop nasal vaccines in progress or to evaluate their benefits. Scientists at the National Institutes of Health and the Authority for Advanced Biomedical Research and Development - known as BARDA - in the United States are examining a number of new generation vaccine concepts, including those that trigger mucosal immunity and could stop transmission.

The process is similar to that used to prioritize female vaccine candidates to receive billions of dollars of investment through the original Operation Warp Speed program in 2020. However, Karin Bok, director of Pandemic Preparedness and Emergency Response at the National Institute of Allergy and Infectious Diseases, warned that they do not yet have the necessary funds.

One of the experts of that Institute is Robert Seder. With their team of collaborators, they test vaccines against variants in animals, and have compared variant-specific vaccines with the original injection of biotechnology company Moderna. Last February they discovered that a regular Moderna booster offered as strong protection against the Ómicron variant in overalls as a specific injection for that variant.

At the same time, Israeli researchers reported that although a fourth injection increased antibodies that block the virus. But it didn't eliminate infections. The vaccinated people who fell ill also had many viruses in their noses. This means that they can infect others. Another study found that a fourth injection did help deter infections, but the effect was short-lived.

Taking into account the current epidemiological situation of COVID-19, available vaccines and boosters, Dr. Seder and his colleagues are now focusing on designing a laboratory experiment that will compare the first nasal vaccines to see which ones are the most promising.

In Georgia, United States, CyanVac is conducting a Phase I trial with 60 patients who have not received other COVID-19 vaccines and who have not had the infection. This nasal vaccine contains a version of a virus that is used to vaccinate dogs against kennel cough and that has been modified to include the spike protein found outside the coronavirus.

The researchers of that company carry out this trial with the idea that the canine virus multiplies for a limited time in people's noses, teaches their immune system to recognize the coronavirus protein and block the true pathogen. The virus used in the vaccine is harmless to humans.

Other vaccine developers use different underlying technologies. In the case of the ArgenVac vaccine, in which Dr. Docena and his team of collaborators work, with support from the National Agency for the Promotion of Research, Technological Development and Innovation (R&D&I Agency), it is developed with two formulations: one would be by injection and the other by nasal route. In order to diagram the production schemes on a larger scale, he also joined the biotechnology company GIHON.

“To develop the ArgenVac vaccine, we used a receptor-binding domain that is the portion of the coronavirus spike protein that binds to human cells. What we do is synthesize it in yeasts,” explained Docena.

“The advantage of a nasal vaccine is that it generates strong immunity localized in the tissue where the virus enters. It also generates a humoral and cellular response. Because resident memory lymphocytes are produced that remain in the mucosa and act faster as a booster dose. In addition, the nasal dose is easier to administer and the rejection of the puncture is avoided,” said Docena.

Vaxart, a company in San Francisco, is testing a pill that contains a harmless version of a virus associated with the common cold. The virus can't make copies of itself. So it can not cause an infection, but it is equipped with the spike protein of the coronavirus and has been shown in the first studies that it generates an immune response in the nose.

In Tanton, in New York, researchers at the Icahn School of Medicine on Mount Sinai developed an intranasal vaccine that is replete with a virus that often causes sneezing, coughing and wing fall in chickens, but has been modified to include the coronavirus spike protein. Researchers at Meissa Vaccines, in California, use a version of the respiratory syncytial virus that has been weakened and covered with the Coronavirus Spike.

The University of Oxford has been testing an intranasal version of the vaccine that its scientists have developed with the company AstraZeneca. In India, Bharat Biotech is also testing an intranasal vaccine. Weeks ago, the Russian Ministry of Health registered a nasal version of the COVID-19 vaccine Sputnik V, which was developed by the Gamaleya Institute of that country.

But getting nasal vaccines to demonstrate greater efficacy and safety over the first generation of inoculants against COVID-19 will be difficult. Maryland biotech company Altimmune halted development of its nasal vaccine for “lower than expected immune responses,” the company announced last year.

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