Intranasal immunization conferred broad-based protection against heterologous respiratory viruses in mice, according to a new study led by Yale's Waldemar Von Zedtwitz Professor of Immunobiology Akiko Iwasaki.
"The highest immune defense occurs at the gate, protecting against viruses attempting to enter," said Iwasaki, the study's principal author.
Mucous membranes have their own immune defense mechanism that fights viruses that are spread through the air or food. When these barrier tissues are challenged, they create B cells, which then secrete immunoglobulin A (IgA) antibodies. IgA antibodies function locally on mucosal surfaces in the nose, stomach, and lungs, unlike vaccinations, which stimulate a system-wide immune response.
While the protective effect of IgA-producing cells in battling intestinal pathogens had been well established, Iwasaki's lab questioned if inducing an IgA response may also result in a localized immune response against respiratory viruses.
They tested a protein-based vaccination designed to jump-start an IgA immune response in mice, working with researchers at Mount Sinai's Icahn School of Medicine. They gave it to animals by injections and intranasally, as is customary with systemic immunization. The mice were then exposed to a variety of influenza virus types. They discovered that mice given the vaccination intranasally were far more protected against respiratory influenza than mice given injections. Nasal vaccinations, but not the shot, produced antibodies that protected the animals against a variety of flu strains, not only the one against which the vaccine was designed.
In animal models, the Yale team is evaluating nasal vaccine strains against COVID strains.
"While both vaccination injections and nasal vaccines boosted antibody levels in mice's blood, only the nasal vaccine allowed IgA release into the lungs, where respiratory viruses must lodge to infect the host," Iwasaki explained.
If the nasal vaccines are found to be safe and effective in humans, Iwasaki envisions them being used in concert with system-wide vaccines and boosters to provide immune system reinforcements at the point of infection.
Key Attributes:
Intranasal vaccines stimulate a broad immune response that neutralizes IgG, mucosal IgA, and T cell responses.
Immune responses at the site of infection (nasal mucosa) are critical for preventing COVID-19 infection and dissemination.
Intranasal SARS-CoV-2 Vaccines:
- Because of the well-organized immune systems of the nasal mucosa, the nasal route has a lot of potential for vaccination.
- Needle-free and non-invasive.
- Ease of administration — does not necessitate the use of skilled health-care personnel.
- Risks linked with needles are no longer present (injuries and infections).
- High compliance (suitable for both kids and adults).
- Manufacturing that can scale to meet global demand.
Protective Efficacy of ChAd-SARS-CoV-2-S Candidate Vaccine in Mice, Hamsters, and Rhesus Macaques:
A single dose of ChAd-SARS-CoV-2-S inoculated mice, hamsters, and macaques provided better protection against SARS-CoV-2 challenge. In all of these animal models, viral clearance was found after infection with SARS-CoV-2 in both the lower and upper airways.
As a result, intranasal immunization with ChAd-SARS-CoV-2-S can trigger an immune response in the nose, which is the virus's point of entry, preventing illness, infection, and transmission. Please see the studies on Hamsters, Mice, and Rhesus Macaques for more information.
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