An Immunologist Fights Covid with Tweets and a Nasal Spray

In the United States and some other countries, the Covid-19 Pandemic has entered a stage in which the coronaviruses has evolved into a highly contagious variant, but the public's attitude has evolved toward indifference, deflating precautionary measures.

Akiko Iwasaki of the Yale School of Medicine is aware of the consequences of the unfinished Pandemic and continues to fight it in the laboratory. Iwasaki wrote in an op-ed column for The New York Times that the world needs next- generation vaccines. Current vaccines against the coronaviruses are effective at preventing disease, but they are not as effective at preventing infections. Iwasaki said that a vaccine in the form of a spray up the nose could change that.

Iwasaki has a group at Yale that is working on such sprays. She and her team are trying to understand why some people are affected by long Covid.

At the start of the Pandemic, Iwasaki rearranged her lab to focus on studies of the coronaviruses, which are related to the H1N1 swine flu. She had looked at how the innate immune system works and how it helps to prime the immune responses.

In March 2020 Iwasaki found that the boundary between her job and her personal life was dissolving because what had been niche topics about immunology with colleagues and students became of great interest to the public. With a lot of reports about Covid flooding the news, Iwasaki became a conduit for the worried and curious who came to her with questions.

She is qualified for both battles because she brings the same fervor to her research that she does on social media. Iwasaki was elected to the National Academy of Sciences and the National Academy of Medicine in successive years. She was elected to the American Academy of Arts and Sciences in the year 2020. The Yale Center for Infections and Immunity will expand her research into diagnoses, treatments and nasal vaccine development.

The evolution of the Pandemic, her efforts to teach the public, and why she thinks the nasal spray may be the new weapon that we need all came up. The interview has been edited to make it clearer.

I think it will change the way we approach vaccines against pathogens, especially those that are coming through the nose. It is possible to apply the same strategy to other respiratory diseases. We need to piggyback on the regular vaccine as a primary vaccine and use the spray as a secondary vaccine.

How would that work?

After someone is injected with one of the available vaccines, you can simply spray a small molecule into their nose. That converts the immunity from the injection to the immunity of the body. Prime and spike is the strategy.

We are taking advantage of the existing immune response that people have from previous vaccinations. That means we don't have to use an extra molecule to get the immune response we want.

Why are mucosal surfaces good places to elicit immune reactions?

The mucus surfaces are the wet surfaces that line your body's internal organs. Unless you are exposed to a mosquito or a tick, most pathogens enter our bodies at this location. It's the first line of defense against diseases.

If mucosal surfaces are a first line of defense to pathogens, why don’t current Covid-19 vaccines target them?

We wonder the same thing. A vaccine is injected into a muscle. The vaccines are able to induce immune responses. They're not designed to give immunity. Right now, that isn't part of the vaccine design. That is something we are trying to change.

It's absolutely true. It is given to people between the ages of 2 and 49. This local immune response is what makes it work well. It is always a risk trying to guess the right vaccine. You know what you need with the coronaviruses.

And that is to target the coronavirus spike protein?

I agree. The spikeProtein is the target but it will change. Instead of chasing the next variant, we want to generate a broadly reactive immune response to the current variant. There is a way to achieve this by using a different spikeProtein. This was done with the use of SARS-CoV-1 spikeProtein.

Would nasal spray vaccines be as effective as the intramuscular vaccines currently being used to battle the virus?

It will be more effective. We still have to test it in humans, but because the spray vaccine establishes local immunity where the virus enters the body, people may not be exposed to the pathogen. You don't have to worry about long Covid if you don't get infections.

You don't have to rely on health care personnel to deliver it because it's a spray. If you get it from your pharmacy, you can administer it yourself. Other countries that don't have the workforce to deliver vaccine may be able to deliver spray. It is very easy to make and can be stored in the fridge for a few months.

I hate needles!

People do. They might be able to use a nasal spray.

Would the nasal spray also somehow build up immunity in the mouth, which is another place through which we can be infected?

Right now, we are looking at that in hamsters. We're hoping to find the answer soon.

The mucus layer blocks the vaccine's ability to be delivered, making it hard to get the vaccine. Most existing mucosal vaccines are based on weakened live Viruses that have their own strategy to penetrate the mucus layer. Our approach does not need live pathogens. A small amount of the spike is enough to cause robust immunity because we are using memory T cells from the previous vaccine.

Are there candidate mucosal vaccines for the coronavirus that are already in clinical trials? When would you predict that such vaccines will be released?

Several are in trials. I hope that some of these can be approved for human use soon.

Your lab is also focused on understanding what causes long Covid, right?

We are attempting to understand long Covid. Millions of people are affected by long covid. Some people get long Covid after infections.

Every organ system is affected by over 200 symptoms. Some people have a few while others have many. Some people do not recover after a few weeks. There are four hypotheses we are testing to see if they are true.

What are the four hypotheses?

It could be an infectious pool of viruses hidden in the body that is causing symptoms, but not leading to a positive test for the disease. Immune system cells could be the cause of the symptoms. It's possible that it's the reactivation of other silent Viruses. Damage from the treatment may turn into a chronic disease.

It's absolutely true. Over the years, people who have been suffering from chronic fatigue syndrome have been ignored. Many doctors think that this is a mental illness, rather than something that is happening outside the brain. This whole viewpoint needs to be changed. There are many other diseases that can lead to these syndromes. This is not a unique feature of Covid.

You quickly became a leading and guiding voice during the pandemic. Did that happen organically?

I like to teach. I teach Immunology at Yale. Teaching is learning as well. I pick up things I didn't know before, so I do a lot of reading to catch up. What we don't understand in immunology is triggered by students' questions. It was natural for me to teach those who are interested.

I used to have a Twitter account where I was talking about immunology, women in science, and other topics. A few immunologists would like the post that I would post about our lab on the social networking site. After the Pandemic hit, there was a huge change in the general public's interest in Viruses and Immunity. People outside of immunology became very interested in our work. People were interested in learning about the immune system and how it works. The transition happened over the course of a year. I think the first thing that put me on the stage was the video I made called "Immunology 101 for non-immunologists", just to explain what the immune system does.

You also do a lot to advocate for women and minorities in science. Where did your passion for that come from?

My mother suffered from this kind of injustice as a child. She worked there. Women were expected to quit their jobs when they became pregnant. Every time she had a baby she was pressured to leave the company. She has been jeered and harassed. She formed a network of other women and men to fight for the right to work, even after quitting the company. I thought that we need to stand up after watching this and hearing about it. There are many stereotypes against women in science.

Is your mom your role model?

She is definitely. My father is also a part of that.

You’re a role model for the younger generation as well. I saw on your Twitter account a photo of a fourth grader presenting about long Covid with inspirational quotes from you.

That was very touching. I liked it very much. People look at me and think about science and immunology. I am amazed that a young person is thinking about long Covid. It's so inspiring for me to see that.

Did you always know you were going to be an immunologist?

I was not aware of that. My parents encouraged me to pursue what I wanted when I was a child. I was introduced to math in high school by a teacher who was passionate about the subject. I decided to go into science instead of literature after I took more math classes. I left Japan when I was 16 because I wanted to see what was out there. After graduating from high school in Canada, I went to undergraduate and graduate school at the University of Toronto, which was a really formative experience for me. I learned about how vaccines work and how they save millions of lives after taking an introductory course there. I wanted to study the immune system.

I hope that's true. Since that time, we have learned a lot. The innate immune system wasn't understood in that class. Charlie Janeway's lab discovered in 1997 that innate signaling through recognition of pathogen-associatedmolecular patterns is what causes adaptive immunity. The way in which the immune system recognizes the pathogen was changed by that. That is the basis of everything else. We didn't know about these things back then. It wasn't taught

Even now, though, how much do we understand the immune system? Are there still major gaps that need to be filled?

Immunology is a very deep field and will never be understood. One of the things that we need to work on is mucosal immunity. Immunology has not gotten a lot of attention. What are the pathways that lead to prostitution? It's not possible to work these things out in the Respiratory Tract.

We’re now in this weird stage of the pandemic, where it feels like it’s over but it’s really not. Where do we go from here?

The evolution of the virus is something that I worry about. We have to think about how we are living if the future variant is very immune-evasive. Many people have decided that Covid is over, and they don't bother to get vaccinations. Those are the people that are going to be most vulnerable to future waves of infections.

Are we ready for the next pandemic?

We aren't responding appropriately to the current Pandemic. People are tired of the swine flu. Regardless of the risk, they are done with it. I would be worried because people are not willing to take any more measures. It's a perfect time for the virus to spread and cause illness. I hope we have some time to relax.

Are you or others in the field worried about the spread of monkeypox? Could it ever become a massive worldwide problem like smallpox was?

I don't know how effective monkeypox can be in becoming a big epidemic like smallpox. If we can put in place testing, isolation, contact tracing and vaccination quickly, we can prevent a massive outbreak.

Would nasal sprays work for monkeypox?

The nose is not a major site of transmission. It can be transmitted via broken skin or other routes. We don't know how many different ways this virus can be transmitted. I don't think a prime-and-spike vaccine is the best way to protect yourself from this virus.