Several teams of researchers are working to develop inhaled anti-COVID-19 vaccines that would induce a line of defense in the upper respiratory tract, where the SARS-CoV-2 viruses enter our body. Such vaccines would prevent infection and, therefore, the transmission of the virus, which would make it possible to quell the pandemic.
At the University of Ottawa, Professor Marc-André Langlois’ team has designed a vaccine in the form of an aerosol that can be sprayed into the nose of people already immunized by the mRNA vaccines currently used.
The mRNA vaccines that are currently being deployed are vaccines given by intramuscular injection that stimulate the immune system in the blood to help it produce antibodies and memory T cells. “These types of vaccines are great at preventing serious disease, but they’re not very good at preventing transmission because that’s not their primary purpose, which is to prevent complications from COVID-19,” recalls Mr. Langlois, director of the Coronavirus Variant Rapid Response Network (CoVaRR-Net).
The COVID-19 virus is a respiratory virus that is transmitted in the form of particles in the air, and the first cells it infects are those of our upper respiratory tract, i.e. the cells of the mucous membranes of the nose, throat and mouth. However, “the immunity induced by intramuscular vaccines does not focus on these places”, he underlines.
The nasal vaccine developed by Mr. Langlois’ team consists of purified viral proteins, more particularly the protein forming the part of the spike of the virus which binds to the receptors of our cells and which is called the binding domain. to the receiver (RBD or receptor binding domain). As this region of the virus is prone to mutations and is often the one that has changed in new variants, a combination of RBDs from different variants has been inserted into the vaccine to provide good protection against all known variants. “The part of the virus that we chose to include in the vaccine is quite large and also includes segments that do not mutate,” says Langlois.
The administration of this vaccine in vaporized form in the nose will induce a local immune reaction in the mucous membranes of the nose and throat. The so-called mucosal immunity that will result will consist of a particular type of antibody called IgA. “Normally mRNA vaccines produce IgG type antibodies which end up in the blood and eventually in the lower respiratory tract, such as the lungs. The IgAs are found instead in the mucous membranes, those of the upper respiratory tract, i.e. at the point of entry of the virus, which allows them to neutralize the virus when it enters the nose and throat in order to prevent it from infecting the first cells. This vaccine would thus prevent infection, ”explains the virologist.
Currently, the CoVaRR-Net team is testing its vaccine in mice. The researchers administer their vaccine nasally to mice that have previously received an intramuscular injection of an RNA vaccine. Their first results are very promising, as they measured “a beautiful IgA-like response in the mucous membranes of the respiratory tract, as well as an increased production (higher than that induced by the mRNA vaccine) of IgG antibodies”. Now the researchers will try to infect the mice with different variants in order to estimate the level of protection offered by this vaccination.
Another innovation presented by this vaccine: the purified viral proteins are produced by plants, which makes it an “easily adaptable technology and allowing very large-scale production at low cost that could be deployed in developing countries”. “This technology can be adapted to other types of coronaviruses and viruses, and it makes it possible to obtain a vaccine that does not require syringes, needles, freezers or the use of a healthcare professional to administer it. “, argues Mr. Langlois.
Other projects
A team from the University of Toronto has already experimented in mice with a nasal vaccine consisting of adenoviruses – purged of their genetic material – which are used as vectors to send the gene coding for the protein into the upper respiratory tract. RBD virus (used in the CoVaRR-Net vaccine). Once administered into the nose, these adenoviruses infect the epithelial cells of the upper respiratory tract which then synthesize the SARS-CoV-2 protein from the genetic material brought by the adenoviruses. The viral proteins thus produced are secreted by the epithelial cells and are then exposed to the local immune system and blood.
In an article published in the journal Cell & Bioscience, Jun Liu and colleagues at the University of Toronto claim to have observed robust mucosal (in the mucous membranes of the airways) and systemic (throughout the body, including the blood) immunity in the form of high levels of IgA and IgG following intranasal administration of two doses of their vaccine. Additionally, after exposing the mice to SARS-CoV-2, they noted the absence of virus in the airways and no inflammation in the lungs, indicating that the vaccine prevented infection.
Researchers at McMaster University in Ontario began phase 1 clinical trials last January to assess the efficacy and safety of their vaccine, which must be inhaled by mouth, in a few volunteers.
“The problem with intranasal administration is that the liquid droplets containing the vaccine remain mainly in the upper respiratory tract, namely in the nose and throat. However, when people become seriously ill from a virus like SARS-CoV-2, the infection takes place in the lungs, particularly in the lower areas of the lungs. An aerosol administered in the mouth travels to these deep areas, in addition to stimulating immunity in the upper respiratory tract,” explains Matthew Miller, professor and researcher at McMaster University.
The vaccine contains DNA from three SARS-CoV-2 proteins, namely spike protein S DNA, as well as viral nucleocapsid and polymerase DNA, two proteins that are not present at the surface of the virus and which, for this reason, “do not mutate much, unlike the S protein, and which are highly conserved not only in the different variants of SARS-CoV-2, but in all types of coronaviruses, including coronaviruses that only exist in bats, but could cause future pandemics,” says Miller. “It is the presence of these last two proteins that leads us to believe that our vaccine could protect against future variants and other coronaviruses that may emerge in humans. »
Studies in mice first showed that intranasal administration of this vaccine induces mucosal immunity, including in the lungs, and also systemic immunity which was found to be surprisingly superior to that elicited by intramuscular injection. of the same vaccine. Given these very good results, the McMaster University team obtained authorization from Health Canada last October to carry out a clinical trial, the first participants of which received the vaccine in January. “If the trial continues to go well and we get the necessary funding, we may be able to complete phase 3 and be ready to submit an application for approval in a year and a half to two years,” says Mr. Miller.
Will these vaccines be the long-awaited panacea that would eradicate COVID-19? Although he believes in the importance of developing such vaccines, Dr.r Don Vinh, a microbiologist and infectious disease specialist at the MUHC, is a little skeptical. “Mucosal vaccines, i.e. targeting the mucous membranes, would eliminate the need for freezers, syringes, needles, alcohol swabs, healthcare personnel. Moreover, if they can generate a response to the virus’ gateway, they could prevent infection and thus reduce transmission and minimize outbreaks. But the mucosal vaccines that exist today, such as FluMist, an intranasal seasonal flu vaccine, and oral vaccines against poliomyelitis, cholera and salmonella that target the intestinal mucosa have not really achieved this goal. , because their effectiveness is very average and variable,” he points out.