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Advantages of Intranasal Delivery of COVID-19 Vaccines

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There are many reasons that an intranasal vaccine against the SARS-CoV-2 virus would be helpful in the fight against COVID-19 infections, University of Alabama at Birmingham immunologists Fran Lund, Ph.D., and Troy Randall, Ph.D., write in a viewpoint article in the journal Science.

That route of vaccination gives two additional layers of protection over intramuscular shots because it produces: 1) immunoglobulin A and resident memory B and T cells in the respiratory mucosa that are an effective barrier to infection at those sites, and 2) cross-reactive resident memory B and T cells that can respond earlier than other immune cells if a viral variant does start an infection.

"Given the respiratory tropism of the virus, it seems surprising that only seven of the nearly 100 SARS-CoV-2 vaccines currently in clinical trials are delivered intranasally," Lund and Randall said. "Advantages of intranasal vaccines include needle-free administration, delivery of antigen to the site of infection, and the elicitation of mucosal immunity in the respiratory tract."

Their viewpoint article goes on to detail the individual advantages and challenges of each of the seven intranasal vaccine candidates. Six are viral vectors, including three different adenovirus vectors, and one candidate each for live-attenuated influenza virus, live-attenuated respiratory syncytial virus and live-attenuated SARS-CoV-2. The seventh vaccine candidate is an inert protein subunit.

Among the drawbacks of using viruses that people may have encountered before is negative interference from anti-vector antibodies that impair vaccine delivery. And because of the minimal risk of reversion for the live-attenuated SARS-CoV-2 virus, it would likely be contraindicated for infants, people over 49 and immunocompromised persons.

"Notably absent from the list of intranasal vaccines are those formulated as lipid-encapsulated mRNA," Lund and Randall said, listing some of the challenges and adverse side effects that accompany that approach.

"Ultimately, the goal of vaccination is to elicit long-lived protective immunity," the UAB researchers concluded. Comparing the benefits and disadvantages of intranasal vaccination against intramuscular vaccinations, they suggest that perhaps effective vaccination need not be restricted to a single route.

"The ideal vaccination strategy," the immunologists concluded, "may use an intramuscular vaccine to elicit a long-lived systemic immunoglobulin G response and a broad repertoire of central memory B and T cells, followed by an intranasal booster that recruits memory B and T cells to the nasal passages and further guides their differentiation toward mucosal protection, including immunoglobulin A secretion and tissue-resident memory cells in the respiratory tract."

Reference: Lund FE, Randall TD. Scent of a vaccine. Science. 2021;373(6553):397-399. doi: 10.1126/science.abg9857

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