Mucosal Immunity

Numerous pathogens can infect the olfactory tract, yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune barrier. Situated in the nasal passages, the olfactory mucosa is directly exposed to the environment to sense airborne odorants; however, this also means it can serve as a direct route of entry from the outside world into the brain. As a result, olfactotropic infections can have serious consequences, including dysfunction of the olfactory system, CNS invasion, dissemination to the lower respiratory tract, and transmission between individuals. Recent research has shown that a distinctive immune response is needed to protect this neuronal and mucosal tissue. A better understanding of innate, adaptive, and structural immune barriers in the olfactory mucosa is needed to develop effective therapeutics and vaccines against olfactotropic microbes such as SARS-CoV-2. Here, we summarize the ramifications of SARS-CoV-2 infection of the olfactory mucosa, review the subsequent immune response, and discuss important areas of future research for olfactory immunity to infectious disease.

An effective nasal vaccine could stop the virus that causes COVID-19 right at its point of entry. But devising one that works has been a challenge for researchers.

Mucosal immunity has a pivotal role in protection from respiratory viral infections.1
The current authors have showed substantial protection from omicron infection by high
concentrations of nasal mucosal SARS-CoV-2 WT spike immunoglobulin-A (M-IgA) over
a 4-week screening period.2 A sharp increase in M-IgA concentrations following BA.1
or BA.2 breakthrough infection in triple vaccinated health-care workers was also observed.2
Here, we present follow-up data with prospectively collected omicron infection rates
and systemic and mucosal antibody concentrations from the same cohort (appendix pp
7–9, 12–14).

Researchers at Karolinska Institutet have shown that nasal drops with IgA antibodies can protect mice from SARS-CoV-2 infection. The results imply a new way to protect individuals at high risk from different variants of the SARS-CoV-2 virus and possibly other infections. The study is published in PNAS.

Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8+ and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data. Nasally delivered live attenuated influenza vaccines (LAIV) have been shown to be effective in vaccine trials yet immune responses are mostly measured in blood. Here the authors report a clinical trial in young adults and measure immune responses in the mucosa and blood to identify compartmentalised responses.

After having successfully tested a mucosal vaccine against coronavirus in animals just months ago, Berlin scientists have now further developed their live SARS-CoV-2 vaccine. Researchers at Freie Universität Berlin have increased the safety of the vaccine, which is administered via the nose. The results of their study on the modified form of the live vaccine have been published in Molecular Therapy.

The nasal cavity is a primary checkpoint for the invasion of respiratory pathogens. Numerous pathogens, including SARS-CoV-2, S. pneumoniae, S. aureus, etc., can adhere/colonize nasal lining to trigger an infection. Secretory IgA (sIgA) serves as the first line of immune defense against foreign pathogens. sIgA facilitates clearance of pathogenic microbes by intercepting their access to epithelial receptors and mucus entrapment through immune exclusion. Elevated levels of neutralizing IgA at the mucosal surfaces are associated with a high level of protection following intranasal immunizations. This review summarizes recent advances in intranasal vaccination technology and challenges in maintaining nominal IgA levels at the mucosal surface. Overall, the review emphasizes the significance of IgA-mediated nasal immunity, which holds a tremendous potential to mount protection against respiratory pathogens.

Virus-specific T cells in the nasal cavity might provide an immediate layer of protection against SARS-CoV-2. This study detected SARS-CoV-2–specific nasal-resi