Nasal Spray Vaccine for SARS-CoV-2

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Science-Based Medicine

Steven Novella, MD

A nasal spray boost may enhance the effectiveness of vaccine defense against COVID.

We are at the beginning of the third year of the COVID-19 pandemic, and while we might nurse some optimism that we are seeing the light at the end of the tunnel, the fact it we still don’t know how long this pandemic will last. Also, experts have essentially abandoned the notion of eradicating the virus, and it now seems extremely likely that COVID will simply be another endemic infection that we will have to deal with, like the flu. Further still, while masking and social distancing are effective, they have their downsides and are not optimal as indefinite strategies to minimize infections.

You know where this is heading – vaccines are by far the best tool we have to beat this pandemic into submission. This, of course, is why vaccine misinformation and vaccine hesitancy are so frustrating. Those who refuse to get vaccinated hurt themselves, hurt everyone else, and are doing it for reasons that are demonstrably false. Aggressive public education and countering misinformation is therefore a critical component to our pandemic intervention strategy.

Meanwhile, it is also helpful to continue to improve vaccine technology, and writing about it can help spread confidence in the vaccines. I wrote recently about the fact that those who had a COVID infection and also get boosted have “super immunity” with ten times the antibody titers and either one alone. Vaccine producers, like Pfizer, are also updating their vaccines to better cover emerging variants. And now researchers are also developing a potential nasal spray COVID vaccine.

The vaccine is remarkably simple, it is just the spike protein of the SARS-CoV-2 virus. That’s it, no adjuvants or other ingredients. The study, which is in preprint, was in mice, in which they compared two groups. One group received only one dose of Comirnaty (the Pfizer-BioNTech COVID-19 mRNA vaccine). The second group received the same one dose of Comirnaty, and then 14 days later received a nasal spray of the spike protein. Both groups were then exposed to SARS-CoV-2. In the first group, without the nasal spray, 80% of the exposed mice died. In the second group, with the nasal spray, none of the exposed mice died. That’s a pretty dramatic result.

The concept of the nasal spray booster is what the researchers are calling “Prime and Spike”. The idea is that you first prime the immune system with a parenteral vaccine. Then you expose that primed immune system to the spike protein in the respiratory tract through the nasal spray. This causes the memory B cells produced by the initial vaccine dose to produce a robust antibody response to the spike protein. The researchers did not test the nasal spray by itself, but that was not the idea of the treatment in any case.

Because COVID is a respiratory illness, in most people the virus enters their system through breathing, the nose, mouth, and lungs. The mucosa of our respiratory tract, which has its own antibodies, is the first line of defense against this route of entry into the body. The nasal spray, therefore, boosts this first line of defense, so that the virus never has a chance to gain entry or establish a foothold.

Obviously this approach needs to be studied in people. Given our experience with the mRNA vaccines, however, there is very good reason to think this nasal spray approach will be extremely safe. The results of this preliminary study are encouraging and suggest the “Prime and Spike” approach may be an effective way to further boost the effectiveness of the existing vaccines. We also need to see if the nasal boost will extend the duration of vaccine protection. A nasal spray may also have fewer side effects, and may garner less hesitancy than an injection. It would be interesting to see how effective the spray is on its own, as it may become a less-than-optimal but better-than-nothing alternative to the jabs.

Following up a vaccine routine with a nasal spray may seem tedious, but it is a small price to pay for the resulting immunity. This is now the world we are living in, given the human population, the density of our cities, our proximity with animal reservoirs of infectious agents, and our global interconnectivity. Unless we want to significantly change one or more of those factors, we will be dealing with frequent pandemics for the foreseeable future. In the last few decades we have had pandemics of HIV, SARS, MERS, and Swine Flu. COVID is only the latest. We have also had the largest outbreaks of serious illness like Ebola. We dodged a bullet with that one – if it had spread into a major city, we could have had another pandemic on our hands. There is one thing for certain, the next pandemic is coming.

Vaccines are our best defense against infectious disease, and we should be grateful for advancing vaccine technology. We simply have to accept that they are going to be an important part of our future. The good news is – they work, and are generally safe. They have the best benefit-to-risk ratio and cost-effectiveness of any medical intervention we have developed.

It’s too early to say if the spike protein nasal spray will become part of the COVID vaccine routine, but it may. In addition to Pfizer, Moderna also announced it is about to start trials of an Omicron version of their vaccine. They are also working on a combined influenza-SARS-CoV-2 booster vaccine. It is very likely that we will need COVID boosters indefinitely in the future to maintain and update our immunity, but perhaps we can still just get the annual “flu” vaccine, which will include the latest variants of SARS-CoV-2. Perhaps then we have to pick up the nasal spray from the pharmacy and take that two weeks later. We have to look at this as routine health maintenance, like getting a checkup annually or going to the dentist every six months.

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking – also called The Skeptics Guide to the Universe.