— It’s time for new approaches to fighting this virus

by Daniel Teres, MD, and Martin A. Strosberg, PhD 

There are currently 20 different vaccines, authorized or approved by various national regulatory agencies, that are achieving their goal in the fight against COVID-19. Countless more are in various stages of development and clinical trials. This goal was (and still is) the prevention of hospitalizations, critical illnesses, and death. But now, the Delta variant is spreading like wildfire, overwhelming our hospitals and intensive care units. And clearly, fully vaccinated individuals who contract the highly contagious Delta variant are still able to transmit live virus. COVID-19 continues to fester and mutate. What might come next, Upsilon? Omega? We have utterly failed to break the train of virus transmission.

There are currently 20 different vaccines, authorized or approved by various national regulatory agencies, that are achieving their goal in the fight against COVID-19. Countless more are in various stages of development and clinical trials. This goal was (and still is) the prevention of hospitalizations, critical illnesses, and death. But now, the Delta variant is spreading like wildfire, overwhelming our hospitals and intensive care units. And clearly, fully vaccinated individuals who contract the highly contagious Delta variant are still able to transmit live virus. COVID-19 continues to fester and mutate. What might come next, Upsilon? Omega? We have utterly failed to break the train of virus transmission.

The Nasal Mucosa and the Chain of Transmission

We need to find new approaches for reducing viral load at the primary portal of entry: the nasal mucosa. Systemic vaccination does not appear to stimulate local mucosal immunity effectively. In the case of a prior infection, you might expect activated nasal IgA to be functional, since infection with the whole virus elicits a broad immune response compared to the mRNA vaccines, which presents just a fragment of the S spike protein. Natural infection starts in the naso-pharynx while systemic vaccines present antigen into the muscle. So, is there an intervention that can effectively stimulate local mucosal immunity?

Intranasal Vaccines

High on the list for reducing viral load and reducing the chance of people spreading the virus should be intranasal vaccines, which would stimulate nasal tissue immune factors (mucosal immunity) including local mucosal IgA.

Daniel Oran, MA, and Eric Topol, MD, from the Scripps Institute published an opinion piece in Scientific American in March highlighting reasons for pursuing intranasal vaccines and for providing financial incentives. As they discuss, these vaccines offer ease of administration and eliminate the issue of “needle phobia.” But these vaccines still need to demonstrate efficacy and safety in clinical trials. For some, there is concern about using an attenuated, live COVID-19 virus and the theoretical risk that the vaccine itself can cause the infection. However, this wouldn’t be the first vaccine of its kind. Flu-mist for influenza is the prime example of an FDA-approved nasal spray for influenza, which uses an attenuated live quadrivalent influenza vaccine. It is approved for people ages 2 to 49, but should not be used for individuals with a weakened immune system.

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