COVID-19 | The vaccines of tomorrow

Vaccines against COVID-19 arrived earlier – and proved to be much more effective – than expected. Then, a booster dose had to be added. Israel is already on its fourth dose. Will these continual adjustments continue? Researchers are working on the next stage of pandemic vaccination.

Mathieu Perreault
The Press

Hybrid immunity

A growing body of research demonstrates that a mixture of vaccines and infection confers longer-lasting protection, at least for infections with SARS-CoV-2, the coronavirus that causes COVID-19. “There is a lot of talk about hybrid immunity, two doses of vaccine and in addition an infection, at the moment”, explains Andrés Finzi, an immunologist from the University of Montreal who has published several studies on the immune response against SARS-CoV. -2.

Jamal Abu-Raddad, from the Cornell University campus in Qatar, is one of those who demonstrated that people who had two doses of the vaccine and one infection were better protected against infections compared to those who received three doses of vaccine, without infection. “Protection against serious diseases, on the other hand, is not better with hybrid immunity than with strictly vaccinal protection, nuances the Qatari immunologist. In fact, the protection of two doses of vaccine against serious diseases is as good as hybrid immunity. Hybrid immunity applies as much to patients who had an infection before their first dose of vaccine as to those who had an infection after receiving two doses of vaccine, says Dr.^r Abu-Raddad, whose work has been published on the preprint site MedRxiv.

Nasal reminder

One of the dominant explanations for the benefits of hybrid immunity is that an infection passes through the respiratory tract. “It may be better to have booster doses nasally,” says Jen Gommerman, an immunologist at the University of Toronto and vaccine manager at the Coronavirus Variant Rapid Response Network set up by the federal government.

The problem is that the respiratory mucous membranes are conditioned not to overreact to unknown substances. “Otherwise, we would have immune reactions every time we eat or breathe substances,” says Matthew Miller, an immunologist at McMaster University in Hamilton, who has developed a nasal vaccine against COVID-19. to be tested in humans by the summer. “We circumvent the problem by using a viral vector; preliminary data are encouraging. Viral vectoring, an approach that uses a harmless virus to carry SARS-CoV-2 proteins, is the technology used by AstraZeneca’s vaccine.

The pancoronavirus vaccine

The other approach in sight is a vaccine that would protect against several coronaviruses. “I would not be surprised to see a pancoronavirus vaccine arrive before a nasal booster dose,” said Matthieu Mahévas, immunologist at the Necker Institute in Paris. He published in December, on MedRxiv, a study showing that the antibodies generated by current vaccines protect against serious diseases attributable to the Omicron variant as well as to the Delta variant. “This is really the next step in the fight against SARS-CoV-2. »

David Martinez, a virologist from the University of North Carolina, published a study last June showing that a “chimeric” vaccine, comprising proteins from different coronaviruses, protected mice against SARS-CoV-1, which causes SARS. of 2003, against bat coronaviruses and against several variants of SARS-CoV-2. “We’re testing it against Omicron,” says Martinez. And we are working with other teams on pancoronavirus vaccines for humans. »

One of these projects involves 24-sided nanoparticles, onto which are grafted as many proteins from different coronaviruses and variants of SARS-CoV-2. One of the problems with this pancoronavirus approach is that it targets less accessible proteins. “The immune system may only have access to these proteins after a cell has been infected,” says Finzi. So we would protect against serious diseases, but not against infection. Mr. Martinez thinks for his part that if the immune response inside the cell is strong, the patient could be vaccinated, but not contagious.

Factories in containers

Vaccine nationalism has been another hallmark of the pandemic. The lack of production capacity in several countries has been pointed out to explain the shortages during the first months of the vaccination campaigns. To overcome this problem, BioNtech, the German company that designed the Pfizer vaccine, will test a “BioNtainer” in an African country in 2024.

It is a vaccine factory with a capacity of 50 million doses, which is manufactured from six standard containers. BioNtech hopes that this standardized approach will allow vaccines to be distributed more quickly, without having to spend several years building a new factory – a process considerably lengthened by regulatory approvals linked to the pharmaceutical industry.

The Russian Flu of 1890

The coronavirus story may generate a small hope. “There is a lot of talk about the possibility that a pandemic in 1890 would have been caused by a cold coronavirus and not the flu,” says Finzi. If so, it could mean that this OC-43 coronavirus started out very deadly, because nobody had immunity, and then it evolved to be more transmissible, but less virulent. In addition, the population found itself having the equivalent of booster doses with annual infections. »

Pierre Talbot, a researcher at the National Institute for Scientific Research (INRS) who studies the neurological effects of the OC-43 coronavirus, thinks this hypothesis about the 1890 pandemic, dubbed “Russian flu”, may well be valid.

OC-43 is one of four coronaviruses to target the common cold. It is similar to a bovine coronavirus which would have decimated European farms at that time. Coronaviruses are responsible for between a quarter and a third of colds.

Five times more speakers

Pierre Talbot has been working on coronaviruses since 1984. “Before the pandemic, less than a hundred researchers attended international congresses on nidoviruses, the category of viruses that includes coronaviruses”, argues Mr. Talbot. These congresses were held only every three years. The latest nidovirus congress, which was due to take place in 2020 but was pushed back to 2021, drew more than 500 attendees, according to its Dutch organizers. “I think we’re going to have a lot more people at our conventions from now on,” says Mr. Talbot.