September 20, 2020

a nasal vaccine against COVID-19


They were a few drops that tasted like strawberry … The polio vaccine was not injected, it was eaten! The news of her eradication in Africa It has filled us with emotion, and memory has brought back the taste of the vaccine. Because vaccines can also be savored. And do they smell?

A few days ago they were published in Cell the first results in the preclinical phase of a vaccine against COVID-19 (yes, another one!) with an important novelty: it is administered nasally. In addition, it eliminates viruses from the upper respiratory tract, avoiding contagion in mice.

Science has built muscle against the pandemic at an extraordinary speed for what is usual. But not only muscle, also creativity. Any proposal is valid, if it is safe and effective.

We are used to using local and fast acting nasal decongestant medications. But how is it possible that this type of vaccine is capable of trigger an immune response in the whole organism enough to defend ourselves from disease?

How a nasal vaccine works

Normally, T cells (lymphocytes) circulate in the blood and lymph. However, when the body produces T cells in response to infection, they can become “memory” T cells. Some of them leave the blood and are located in the organs that can potentially be attacked by this infection (for example, in the lungs in the case of respiratory viruses), in the form of “resident” T cells.

These cells are usually housed in mucous, the tissues that line the respiratory tract and many of the internal organs that are in direct or indirect contact with the outside, such as the nasal and oral cavity and the lung. There they wait to react against the infection.

Diagram of the development of the vaccine with intramuscular and nasal administration published in Cell. Adapted by N. Campillo and M. Jiménez.

The vaccine they are investigating at the University of Washington School of Medicine (USA) is based on a chimpanzee adenovirus that expresses the coronavirus protein S (similar to the vaccine being developed at Oxford). This protein, remember, is responsible for the penetration of the virus into the cells of the mucosa of the upper respiratory tract and lungs. The chimpanzee virus cannot replicate in humans.

What happened when the researchers injected one or two doses intramuscularly into mice expressing the human ACE2 protein (the protein through which the virus enters human cells)? That rodents produced antibodies IgG (typical antibody response in fluids) and T cells in blood. When inoculating them with the virus, they observed only a reduction in lung infection. That is, they found RNA of the virus in the lungs (they contracted the disease in a milder way) and in the upper respiratory tract (they could spread the disease). Furthermore, they did not detect specific T cells in the pulmonary mucosa.

The observed effect changed radically when the vaccine was administered nasally. In that case, they detected IgG type and type IgA (typical antibodies of the response at the mucosal level), in addition to “resident” T cells in the lungs. The so-called “mucosal immunity” was produced, which can be much more protective against respiratory infections.

As if this were not enough, when inoculated with the SARS-CoV-2 virus, they detected very little RNA of the virus in the upper respiratory tract and nothing in the lungs. This implies that, administering it through the nose, the transmission of the disease would be significantly reduced, by preventing individuals from spreading the virus

New lives for old drugs

Finding different uses for drugs is a strategy to try to reduce the costs of the drug. drug development (on average $ 1.3 billion and about 15 years).

One of them is repositioning, which is the process of finding a new therapeutic use for an already known drug. Another is reformulation, which consists of developing different formulations for the same drug. For example, Finasteride Initially it was prescribed to treat the symptoms of benign prostate hyperplasia and now it is also prescribed at different doses for male hair loss. And so many examples can be found in pharmacies.

In the case of the nasal vaccine, changing the route of administration can add different characteristics, such as more effectiveness and better tolerance.

The way of entry counts

Nasal administration is not entirely new. There is already a flu vaccine given through the nose, which uses a weakened form of the flu virus. Something similar happens with polio vaccines, although the most used currently is the injectable version.

One of the three vaccines being developing at the CSIC, still in the preclinical phase, also contemplates nasal inoculation if it turns out to be more effective.

What has been proven so far is that this option works for mice. However, it must be taken into account that the functioning of the immune system of mice is quite different from that of monkeys and humans. The next step will be to test the vaccine in non-human primates, whose immune systems are more similar to ours. Yes it is effective and safe will advance to phases I, II and III.

This vaccine is one of the most delayed, but who knows if it will not be the one that helps us eliminate the coronavirus more efficiently and safer. More comfortably, of course it is.

This article was originally published on The Conversation. You can read it here.

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