NIH Launches First Trial Of Nasal COVID Vaccine

"Taking a new step, uttering a new word, is what people fear most.”
― Fyodor Dostoevsky, Crime and Punishment

Earlier in these pages I described how the mucosal immune system is different from the general immune system of the body. Your mucosa (i.e., the lining of your nose, mouth, throat, sinuses, lungs, etc.) has its own robust immune defense and produces different types of antibodies in response to invaders. The nose, mouth and throat are often the first line of defense to airborne pathogens, such as the flu and SARS-CoV-2 viruses. So, when you are infected via the mucosa by an airborne pathogen, it activates a local immune response while eventually sounding an immune alarm for the body-whole. But by the time the infection settles in and the rest of your body responds, it is all-out immunological warfare and you feel crappy (hope I am not being to technical). Sometimes the bug wins too. Too often, especially before we had the vaccines, COVID won, and folks were hospitalized in dire straits with tubes attached to machines keeping them alive, too often failing.

The amazing vaccines we developed in record time were delivered into an arm muscle to stimulate our general body immune response, not our mucosal immunity. This meant that even though we had immunity, the virus could still enter us, set up shop and wait until the general body immune reinforcements arrived. Those reinforcements were quite effective at preventing serious disease, but you still would get ill.

Wouldn’t it be nice if a vaccine could be developed to nip the infection in the bud at the site of entry--in the mucosa--so it could not set up shop at all? That is an idea that has been percolating in the minds of immunologists for a while. It is the idea behind a mucosal vaccine that I described earlier.

But, if it is such a good idea for the CoV-2 coronavirus, why not for flu or other airborne pathogens that have been around much longer? Indeed efforts to develop nasal vaccines for influenza have been ongoing for a couple of decades. But, when is the last time you got a nasal spray vaccine for the flu? The track record has been mixed. The FluMist nasal flu vaccine was approved for kids in 2003. Initially it was a convenient alternative to the injected vaccine. But, it showed limited efficacy in adults. Early on it was deemed just as effective as the standard vaccine in kids, not better as hoped. More recently it was reported to not be so effective. As a result it is no longer recommended by the American Academy of Pediatrics. It clearly did not rise to the hope we had for a nasal flu vaccine.

All the above negativity for the early nasal flu vax doesn’t mean that the idea of a nasal flu vaccine is invalid. Researchers will test different sorts of flu antigens for the nasal approach. FluMist used a live, but attenuated virus in its nasal vaccine. That means kids snorted a live virus that could infect cells but not cause disease. Perhaps a different flu antigen would be more effective? But, frankly, it is hard to get more realistic than a live-attenuated virus.

Nevertheless, another promising new flu nasal vaccine candidate is FluGen’s, M2SR, developed by researchers at the University of Wisconsin-Madison. This vaccine is a bit different because it uses a wholly live virus with an essential replication gene deleted from its DNA. This means the virus is fully functional except it can’t replicate and cause illness. That makes it a little different from the live-attenuated virus. It should stimulate the immune system like a natural infection, but begs the question: how will that be different from the immune response generated from a live attenuated virus? How will that crippled snuffed virus stimulate a different immune protection from the sniffled FluMist attenuated virus? We will see, won’t we? That is why we do such experiments.

Back to COVID. This summer, NIH launched the initial Phase 1 trial to begin testing such a nasal COVID vaccine.

The vaccine. The vaccine is a mouse virus (MPV) in which a piece of the CoV-2 spike protein is expressed. MPV does not cause human disease but does like to stick to human and primate mucosal epithelial cells and should be an effective vector for delivering the spike protein sequence where it can tickle an appropriate immune irritation. In animal studies, the experimental virus was safe and produced a robust immune response in the mucosa lining the nose and respiratory tract of experimental animals. All very encouraging, hence the move to human trials.

The human trial. This is a Phase 1 trial, the first step of any experimentation in humans. Phase 1 trials do not look for efficacy and are done on quite a small number of patients, anywhere from 20-100 subjects who are not tested at all for resistance to the disease. The purpose simply is to look for common safety issues like whether the vaccine causes a general adverse reaction with increasing doses and how well it induces an immune response (i.e., anti-spike protein antibodies) at different doses. Using this information, a Phase 2 study can be designed including more subjects, usually hundreds. This begins to look for more subtle side effects and is the first test of the ability of the vaccine to protect against COVID disease. This would be a controlled trial where experimental vaccine recipients are compared to a control cohort who do not get the nasal vaccine, but probably a placebo. If data collected from this study warrant, then a Phase 3 study is done on thousands of patients to further refine the safety and efficacy profile of the vaccine.

The Phase 1 study that is underway is being led by the National Institute of Allergy and Infectious Diseases and is enrolling 60 subjects at trial sites, which include the Baylor College of Medicine, Houston; The Hope Clinic at Emory University in Atlanta; and New York University on Long Island. The immune responses of volunteers will be followed for one year. So, it will be a while before investigators have the data to begin Phase 2 trials.

Bottom line. This is just the beginning and it will take several years to finish. If successful, this would represent the next generation of COVID vaccine. Finally, as I have often ended my blog posts…

…we will see.

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