COVID Booster Shots Administered in the Nose May Be Better Than the Arm

New research suggests that COVID-19 vaccines that are delivered through the nose—referred to as intranasal vaccines—can offer even more protection than intramuscular injections given in the arm. And as the possibility of booster shots looms ahead, there is heightened interest in a nasal spray replacing a needle.

Two professors from the University of Alabama at Birmingham, Troy Randall, PhD, and Fran Lund, PhD, build the case for using experimental intranasal vaccines in a review article published in journal Science in July.

While there are nearly 100 experimental COVID-19 vaccines now in clinical trials, only seven intranasal vaccines are currently being developed. Randall and Lund reviewed data on all seven. Six of these vaccines use a harmless live virus, called a vector virus, to deliver the COVID-19 virus into the nose. These are called “live attenuated” vaccines, since they use a live, but weakened form of the virus to trigger an immune response without causing illness.

“Scientists could make a mild form of influenza, but replace some of the influenza proteins with SARS-CoV-2 proteins," Randall tells Verywell via email. "The vector could then infect the nose, without causing illness, and trigger an immune response to SARS-CoV-2."

The seventh vaccine candidate is a type of vaccine called a subunit vaccine. It uses specific protein pieces, called subunits, of an inactive SARS-CoV-2 virus, which have been specially selected for their ability to stimulate immune cells. 

Targeting the Nose

A major benefit of intranasal vaccines is that the vaccine is delivered to the site of the infection—the nose.

“Infection occurs in the nose, so we want the immune response concentrated in the nose,” Randall says.

The intranasal vaccines work by stimulating antibodies, which are proteins that are produced by the immune system to fight the SARS-CoV-2 virus that causes COVID-19. Specifically, these vaccines create more immunoglobulin A (IgA) proteins, which are types of antibodies that protect mucous membranes in the nose.

The intranasal vaccines also boost the production of memory B cells and T cells in the nose, Randall says. These cells protect against COVID-19 by making more antibodies and providing an extra layer of defense in case a person is exposed in the future.

“This direct protection in the nose can prevent the virus from ever getting deeper into the body to infect the lungs,” Monica Gandhi, MD, MPH, professor of medicine and associate division chief in the division of HIV, Infectious Diseases and Global Medicine at the University of California, San Francisco, tells Verywell.

While Gandhi was not affiliated with the study, she said "you will be less likely to spread the virus to others if you have effective immune defenses in your nose.”

In addition to potentially being more effective against viral transmission, COVID-19 vaccine sprays would be a preferred option for those who are afraid of shots. Offering a nasal spray instead of a prick in the arm would not only ease anxiety for needle-phobic people when they get the vaccine, but it could also boost the overall number of vaccinated people. A new study from the U.K. found needle phobia to be the cause of COVID vaccine hesitancy in about 10% of its population.

The Downsides of Intranasal Vaccines

There are some drawbacks to these intranasal vaccines. The live-attenuated vaccines contain a live, but harmless, form of a virus (such as a cold or flu virus) to boost the immune response. If people previously had the same type of cold or flu virus that is used in the vaccine, then it means they already have this type of antibodies in their body and it would render the antibodies in the vaccine useless.

Because live-attenuated vaccines contain a small amount of the weakened live virus, this type of vaccine should not be used in infants, the elderly, and the immunocompromised.

What's the Best Way to Vaccinate?

Experts believe that the ideal vaccination strategy would be to first deliver the vaccine into the arm, followed by a vaccine booster administered into the nose.

“Having both types of immunity—systemic and nasal—will protect the entire respiratory tract,” Randall says.

That’s because each of these delivery methods boost immunity against the SARS-CoV-2 virus in different, yet important ways. Since an intramuscular vaccine triggers systemic immune responses in the bloodstream and lymph nodes, it protects the lungs, but not the nose. In contrast, intranasal vaccines trigger an immune response in the nose to protect the nasal passages.

“The fight against COVID is complicated and should evolve as data and variants evolve,” Gandhi says. "Intranasal vaccines at this point would be an excellent addition to our defense against the virus and should be moved along quickly in clinical trials to market.”

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.