Nasal vaccine boosters can trigger strong immune defenses in the respiratory tract, study finds

Nasal vaccine boosters can trigger strong immune defenses in the respiratory tract, study finds

Most vaccines - and boosters - are injected directly into muscle tissue, usually in the upper arm, to prime the body's immune system to fight the disease. However, for respiratory diseases like Covid-19, it can be important to have protection right where the virus enters: the respiratory system.

In a new study, Yale researchers found that nasal vaccine boosters can trigger strong immune defenses in the respiratory tract, even without the help of immune boosters known as adjuvants. The results, researchers suggest, could provide critical insights into developing safer, more effective nasal vaccines in the future.

Our study shows how a simple viral protein antigen can increase respiratory immune responses against viruses. These data imply that viral proteins in the nasal spray can be used to promote antiviral immunity at the site of viral entry. “

Akiko Iwasaki, Sterling Professor of Immunobiology at Yale School of Medicine (YSM) and senior author of the study

The study was published in the journal Nature Immunology. The first author is Dong-Il Kwon, a postdoctoral fellow in Yale’s Department of Immunobiology.

For the study, researchers first injected mice with a traditional mRNA Covid-19 shot injected directly into the muscle. The team then gave the mice a booster vaccine through their noses. The team specifically wanted to evaluate the effects of vaccine boosters that do not contain special ingredients called adjuvants. Adjuvants are used in some vaccines and stimulate a stronger, longer-lasting immune response, but they can also cause adverse effects such as inflammation and swelling of facial nerves.

"We call this vaccine strategy 'prime and spike,' where the mice were primed with mRNA vaccines intramuscularly, followed by a nasal boost with unadjuvant spike protein," said Kwon, a member of Iwasaki's lab.

The Yale-developed “prime and spike” approach jumpstarts immune response in the respiratory system—the first part of the body infected by Covid-19. “Prime” refers to the process of administering a traditional intramuscular vaccine shot, while “spike” refers to a follow-up vaccination delivered nasally — usually in the form of a spray containing coronavirus-derived spike proteins.

After the first shot, immune cells were primed in the mice's lymph nodes. After the nasal booster, B cells migrated from the lymph node to the lungs and produced immunoglobulin A (IGA), an antibody that protects the nose and lungs from infection. Memory CD4+ helper T cells acted as natural adjuvants by recruiting B cells and helping them clear IgA in the lungs.

Only the nasal booster triggered this strong local immune response, the researchers found. Boosters given other options, including intramuscular injection, did not produce much IGA or activate immune cells in the mice's lungs. When the researchers gave the mice a second nasal booster, their IGA levels increased even more in both the lungs and nasal passages.

"These findings explain why nasal boosters do not require adjuvant to induce robust mucosal immunity at the respiratory mucosa and can be used to design safe and effective vaccines against respiratory viral pathogens," said Kwon.
Normal Covid-19 shots do not produce much IgA in the nose and lungs. So people can still be infected or pass it on even if they are vaccinated. However, this study shows that nasal boosters can trigger strong, long-lasting immune protection against respiratory diseases like the first attack of Covid-19.

“Understanding how this safe and simple nasal enhancer promotes protective mucosal immunity makes it easier to develop this approach for human use in the near future,” Iwasaki said.

Iwasaki is also a professor of dermatology and molecular, cellular and developmental biology in the Yale Faculty of Arts and Sciences, a professor of epidemiology (microbial diseases) at the Yale School of Public Health, and a Howard Hughes Medical Institute investigator.

Other Yale authors include Tianyang Mao, a former graduate student who is now a postdoctoral fellow at the Broad Institute of MIT and Harvard. Benjamin Israelow, assistant professor of medicine (infectious diseases) at YSM; Keyla Santos Guedes de Sá, a postdoctoral researcher; and Huiping Dong, a research associate.

This study was supported by grants from the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute.

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