The world is coming to terms with the fact that Covid-19 is here to stay two years after the outbreak. Millions of people are still falling ill as new strains emerge. coronaviruses shots are one of the greatest medical achievements of all time, reaching the market in less than a year and saving millions of lives, but anyone who received three doses and still got infections will understand that the virus is a resilient opponent.

Marty Moore thinks he can beat it.

Moore, the relentlessly upbeat founder of Meissa Vaccines Inc., says that Covid isn't just a sprint, it's a marathon.

Moore is one of a growing group of virologists who want to spray vaccines up people's noses. The advantage of that approach is that it can cause the body to fight illness much faster than an injected vaccine can, and that's what they argue.

relates to Why Nasal Sprays Are Poised to Be the Next Weapon for Fighting Covid

Christian Drosten said there were only two ways to stop the spread of the disease. He said that the alternative would be to have a live vaccine that is sprayed in the nose or throat. Moore says to put guards in front of a building rather than inside it to build protection where the battle begins.

The first human test of a vaccine against respiratory syncytial virus, orRSV, was to begin in early 2020. Moore was able to retool his product to bring the coronaviruses to heel. Moore expects to have results from human trials of a candidate formula by the fall. If regulators fast-track it as they did the first round of Covid vaccines, it could start going into noses within a year. Moore says he's more convinced that nasal sprays can do the job now that he's made progress. We don't accept it.

Structural challenges ranging from the scientific to the economic to the logistical are what will have to be overcome for any Covid vaccine to make a difference. The effectiveness of the Pfizer-BioNTech and Moderna shots against infections fades as time passes and new variations emerge. He says that future vaccines should offer improvements when it comes to tolerability, length of protection, or ability to block infections.

He insists that nasal sprays can help, though they are difficult to pull off. It is relatively easy to get a precise dose of medication by sticking a needle in someone's arm. It's difficult to get the right amount with a squirt up the nose because of the body's thicket of natural defenses: nostril hairs, sneezing, and the dense layer of mucus that lines the respiratory tract.

Only a half-dozen of the Covid vaccines are nasal sprays, and that's because of the challenges. A team in China is using an influenza virus filled with genetic instructions for making a piece of the coronaviruses spike, which the body learns to attack. The company that makes the Covid shot uses a primate adenoviruses to deliver the genetic information. Codagenix Inc., a New York-based company, and the Serum Institute of India, a New Delhi-based company, are working together on a weakened version of the coronaviruses strain.

Meissa's candidate uses a weakened virus to do the dirty work, making it a live-attenuated vaccine. The advantage of this is that the viruses are able to penetrate the body's defenses. To make sure they are safe, they must be weakened. That is no simple feat. They won't get an adequate immune response if they're too weak. The weakened virus must never evolve to the point that it will make a person sick. In recent decades, the pharmaceutical industry has focused on alternatives such as introducing only a piece of a virus, even if these approaches aren't always as powerful. Paul Offit is the director of the Vaccine Education Center at the Children's Hospital of Philadelphia.

Even if you clear the hurdles, it's still hard to get people to buy a vaccine. FluMist is the only one ever to make it to market. It failed to live up to the predictions that it would dominate the field. The flu virus can only be reproduced in the cooler temperatures of the nose, not the lungs or other parts of the body. The biggest chunk of the flu vaccine market is for people older than 50, and regulators are reluctant to recommend it to them.

It has been difficult for startups to break into a business that has been dominated by a few companies. To start selling a product, companies need to clear an extremely high bar in terms of safety and show superiority over existing options. The Pandemic blew open that dynamic, catapulting technologies such as messenger RNA to center stage. Moderna and Germany's BioNTech co-developed a product with Pfizer. It has allowed smaller players to compete in a market that is expected to reach $50 billion by the year 2025. Even though his company is small, Moore says he can win a piece of that business.

Understanding what happens when a coronaviruses enters you is important to appreciate the promise of sprays. First, messenger cells capture bits of the virus from your airway, and then make an hourslong journey to the nearest luminary to warn of the invader. B cells and T cells are ready to fight back if you have had your Covid shots. The weapons begin a slow journey through the body in search of the virus. This works well in preventing severe Covid, but it takes a couple of days to play out, so people often get sick before they know it.

A spray in the nose might be more accurate in mimicking the natural protection a person gains from an illness. The Covid- ready B and T cells are put in the nose and throat after the immune system encounters the virus. It fosters the development of IgA, which takes up residence in the mucus lining and can stop the virus from ever reaching the cells lining your airways. Only a vaccine that enters the body as a virus can give you that. The added protections give the immune system an advantage of as much as a day and a half in fighting Covid.

Live-attenuated vaccines are so effective at getting to the most important cells that they work best with anasal delivery. Meissa uses a new way of attenuating a virus that can uncouple it from the safety-vs-efficacy seesaw. The approach is inspired by the work done withRSV, which has been weakened not by making it harder for the virus to replicate, but by genetically removing its ability to hide from the immune system. If you block the blocker, then you unleash the immunegenic potential of that virus, in theory, you could get dosed with a large amount of this mutant version ofRSV, generating a massive immune response while posing little to no threat of making you sick.

Meissa stuck the coronaviruses spike protein onto the shell of the vaccine. In tests on monkeys, the company's product was found to protect them from the virus. Preliminary data from a clinical trial in 130 people show no serious safety problems, which is an indication that the virus has been well mitigated. A single dose stimulated about the same level of IgA antibodies as what has been seen in people with Covid.

The company expects to have full results from the human trial this year. It plans to study it in children soon after adding participants to test it as a booster. The product is suited to kids as they tend to be afraid of needles and they play a big role in spreading respiratory diseases.

In lab studies, Meissa's vaccine has offered significant protection against the alpha and beta variant. Moore says the vaccine's ability to protect against a range of strains may be due to its physics. The live-attenuated approach sends the coronaviruses spike right into the wilderness of the body. It gets bent like a virus as it tries to get to cells. This exposes the immune system to a full picture of the spike in action, giving it better coverage.

Moore was a graduate student at the University of Georgia when he was fixated on respiratory viruses. In the early 2000s, a distinguished professor stood up and said, "Nice work, Marty," as he was presenting his research into a type of adenoviruses. Next time, pick an important virus. He holed up in a library and built a spreadsheet to identify the Viruses that affect humans but get little attention. Two candidates were revealed in his analysis. The first was a coronaviruses that had just emerged in China. Within a few months, that disease would disappear. The second was the same as the first.

Almost everyone is affected by the disease by their second birthday. It can be dangerous for young children with their smaller airways if they get a common cold. After landing a faculty position at Emory University in Atlanta, Moore developed a platform for dissection of the virus that he created during his research at Vanderbilt University.

Scientists were stuck when it came to making vaccines. The approach backfired when they tried to give infants an inactivated form of the virus. They abandoned their efforts to create a live-attenuated vaccine because it no longer elicited a strong immune response when weakened.

Moore came up with a new approach. The current coronaviruses has nothing to do with the fact that they are a key factor influencing us. The immune system is unable to see that it is there. He wondered what would happen if you removed the proteins that let RSV sneak in. You could spray that genetically engineeredRSV into the nose, leading the immune system to kill it. The weapons would remain in the nose and throat for a long time. It would be a new way to deliver a vaccine.

A big pharma company offered to license the technology, but Moore wanted to develop it himself. He started Meissa Vaccines because of the star in the constellation that forms the mythical hunter's head. Moore was able to apply for federal business grants after landing a spot at the JLABS in San Francisco. They quit their jobs to focus on Meissa. Moore moved his family to California and devoted himself to raising funds, while Tang spent his days in the lab trying to prove that Meissa's genetically modified version ofRSV could make for a safe and powerful vaccine.

The company got $30 million from a venture capital firm and filed paperwork to start clinical trials. Moore had a plan to move into a bigger office after a hiring spree made things crowded in the tiny space. As 2020 began, Meissa was on the verge of spraying the first dose of his vaccine into a human, a culmination of his life's work.

You're going to need this, and you're going to want it.

Moore woke up at 4 a.m. on a Saturday in January. He settled in behind a desk that had once belonged to his father under a yellow streetlight. Moore downloaded the code after scientists posted the genome sequence of a novel pathogen. He put it into his laptop and arranged four rows of genetic sequence on top of each other. Moore was shocked when his eyes scanned a portion of the spike's genetic makeup that suggested the virus could quickly latch on to human cells.

Moore feared he might jeopardize everything he had been chasing for two decades with the new virus as he pondered developing a vaccine. The stakes were obvious and overwhelming. He thought that the coronaviruses would be with us for a long time and that few scientists would attempt to stop it with a spray. He sketched out how he might insert the coronaviruses spike into the platform.

Moore settled on various virus constructs that might work as a vaccine as patients around the world flooded hospitals. The crucial step was attaching most of the coronaviruses spike to the root of the surface proteins. The candidate would be useless without this connection. The Meissa team translated the models into a genetic sequence and ordered a small amount of the solution from a supplier.

Moore phoned Tioni to see if she'd be willing to come into the hospital. She, Tang, and Moore were wearing N95 masks, smocks, and hair covers after she said yes. They would change their clothes in the garage and sleep alone.

relates to Why Nasal Sprays Are Poised to Be the Next Weapon for Fighting Covid

When the samples arrived, the trio injected them one by one into the cells. It can take days for the cell to start pumping out copies of the genetically engineered virus. The team put a red marker on the virus to see if it is spreading. Meissa's first few attempts showed no glow, fueling fears that the idea wasn't going to work. Moore peered into a microscope, focused the lens, and saw a sea of red after injecting a candidate. The team planned the animal experiments needed to convince regulators that the vaccine was safe and promising enough to justify testing on humans.

Pfizer and Moderna had begun human trials for their candidates, and governments began directing their resources to the leaders. When the companies presented data showing their vaccines were more than 90 percent effective, many people proclaimed the end was near.

Moore was happy that his rivals had developed their vaccines so quickly, and he was looking forward to getting his own shots. He didn't agree with the idea that the epidemic was almost over. Even as deaths have fallen by half globally in the past year, daily infections have roughly doubled, a testament to both the strengths and limitations of Covid shots. The bar for new candidates has gone up because they have to compete with established products.

There is a reason to believe that nasal sprays might be effective boosters for people who have been exposed to Covid. The immune system in these people will already have B and T cells, so only a small amount of a vaccine would need to penetrate the nose.

Moore acknowledges there is a long road ahead to prove his Covid candidate is safe, effective, and superior in at least some respects to the shots. If the trial results are good, the next step would be larger tests, which can cost hundreds of millions of dollars.

Moore will be able to increase his staff to 25 people because of Meissa's relocation. They are doing early work on fighting two other respiratory viruses and have expanded the study of their candidate into infants. Even if Meissa's spray arrives too late to have a big impact on Covid, the company aims to be prepared to quickly make a vaccine in response to the next Pandemic. Moore believes there is enough reason to build immunity against Covid in the nose and throat. He says that if you want to stop hitting the snooze button, you can.