The discovery of COVID-19 variants such as delta and omicron has prompted scientists to assess the efficacy of existing vaccines and boosters against novel strains of SARS-Cov-2.

According to Yale’s Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology, a novel reaction to the fast-changing virus may be located right at the gateway to our lungs.

In a new study, she and colleagues discovered that intranasal vaccination gives widespread protection against heterologous respiratory viruses in mice, whereas systemic immunization, which involves an injection to induce systemic immunity, did not.

“The best immune defense happens at the gate, guarding against viruses trying to enter,” says Iwasaki, senior author of the study.

Mucous membranes carry their own immune defense mechanism that protects against diseases that are transmitted through the air or food. When these barrier tissues are stimulated, they create B cells that secrete immunoglobin A (IgA) antibodies. Unlike vaccines, which induce a systemic immune response, IgA antibodies act locally on the mucosal surfaces of the nose, stomach, and lungs.

While the protective effect of IgA-producing cells against intestinal infections was well established, Iwasaki’s laboratory questioned if inducing an IgA response may also result in a localized immune response against respiratory viruses.

Scientists tested a protein-based vaccine engineered to jump start an IgA immune response in collaboration with researchers at the Icahn School of Medicine at Mount Sinai in New York, delivering it to mice by injections, as is normally done with systemic immunizations, and also intranasally.

They then inoculated mice with several influenza virus strains. They discovered that mice given the vaccine intranasally were significantly more protected against respiratory influenza than mice given injections. Nasal vaccines, but not the shot, generated antibodies that protected the animals against a variety of flu strains, not simply the strain against which the vaccine was designed.

In animal models, the Yale team is currently evaluating nasal vaccine strains against COVID strains.

While both injectable and nasal vaccines boosted antibody levels in mice’s blood, only the nasal vaccine permitted IgA release into the lungs, where respiratory viruses must lodge in order to infect the host, Iwasaki explained.

If the nasal vaccinations are found to be safe and effective in humans, Iwasaki anticipates them being used in combination with currently available vaccines and boosters that function systemically to reinforce the immune system at the site of infection.

Source: 10.1126/sciimmunol.abj5129

Image Credit: Getty

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