COVID-19 Resource Center

COVID-19 Resource Center


Healio Interview.

Disclosures: Randall reports being a consultant for and receiving research funding from Altimmune.
July 22, 2021
2 min read

Q&A: The case for an intranasal COVID-19 vaccine


Healio Interview.

Disclosures: Randall reports being a consultant for and receiving research funding from Altimmune.
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According to scientists from the University of Alabama at Birmingham, only a small number of COVID-19 vaccines in development are given as nasal sprays, despite the technology’s potential to block SARS-CoV-2 transmission at the source.

“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,” Frances Lund, PhD, and Troy D. Randall, PhD, wrote in a viewpoint published today in Science.

Healio spoke with Randall to discuss the potential advantages and disadvantages of an intranasal COVID-19 vaccine.

Healio: What would be the advantages of an intranasal COVID-19 vaccine?

Troy D. Randall

Randall: One advantage is needle-free delivery, which is helpful for those persons who hate needlesticks. It may — depending on regulatory approval — mean that vaccines could be administered by oneself or by someone who is not trained to perform intramuscular injections. That might make it easier to distribute and administer the vaccines. Another advantage is that intranasal delivery will administer the vaccine to the site most likely to be exposed to infection. Some aspects of the immune response occur locally, and having immunity in the nose should better protect against respiratory infection.

Healio: What would be some of the drawbacks?

Randall: The biggest drawback is that to be effective, the vaccine has to get across the epithelium. A needle just pokes through the skin, but intranasal vaccines use either vectors — attenuated viruses that infect the epithelium — or proteins that bind to receptors or cell types that drag the vaccine antigens across the epithelium.

Healio: Of the seven intranasal SARS-CoV-2 vaccines in development, three use a live-attenuated virus — one an influenza virus, one a respiratory syncytial virus and the other a SARS-CoV-2 virus. What are the benefits of this technology, and what are some of the issues that could make these vaccines less effective?

Randall: The live-attenuated viruses are all based on respiratory viruses that normally infect humans. Because they are attenuated, they will not cause disease, but they will infect respiratory epithelial cells and trigger an immune response. However, people may already have been exposed to those viruses and have antibodies against them that prevent infection. Those antibodies could also prevent or reduce the efficacy of the vaccine.

Healio: Additionally, there are three virus vector vaccines and one protein subunit intranasal vaccine in development. What are the benefits and drawbacks of these, and is one of the three technologies listed so far more promising than the others?

Randall: The virus-vectored vaccines are similar to the live-attenuated vaccines mentioned earlier, but rather than just being attenuated, the vectors cannot replicate at all. Again, they are based on viruses that can infect humans, so some humans may have antibodies against the vectors that reduce the efficacy of the vaccine. The protein subunit vaccine cannot be neutralized by pre-existing antibodies, but it has to get across the epithelium to cause an immune response.

Healio: Can messenger RNA vaccines be delivered intranasally?

Randall: Messenger RNA vaccines have been intranasally delivered in rodents and generated good immune responses. In theory they can be given intranasally to humans, but I have not seen reports on how well they work. They may need alternative formulation to get across the epithelium effectively.


Lund FE, Randall TD. Science. 2021;doi:10.1126/science.abg9857.