Research by Yale University researchers showed that intranasal vaccination can provide mice with extensive protection against heterologous respiratory viruses, while systemic immunity that uses injections to cause systemic protection cannot. These studies focusing on the prevention of influenza infection show that intranasal immunity, rather than systemic immunity, induces the secretion of IgA from antibody-secreting cells (ASC) in the lung mucosa, thereby preventing secondary attacks by the same or different strains. flu virus. The authors, led by Dr. Akiko Iwasaki of Yale University and Waldemar Von Zedtwitz Professor of Immunobiology, said when reporting on their research in scientific immunology. "Our results show that local rather than systemic immunization with influenza virus induces the resident ASC in the lung mucosa to secrete IgA, which provides strong protection and cross-protection for the secondary attack of influenza virus." As Iwasaki further pointed out In that way, "the best immune defense occurs at the door, preventing the virus from trying to enter."

Iwasaki further suggested that these findings also indicate that an immune response to the rapidly mutating SARS-CoV-2 virus may be found at the door of our lungs. The Yale University team is currently testing a nasal vaccine strain against the COVID strain in an animal model. The title of their paper is: "Intranasal priming induces local lung resident B cell populations and secretes protective mucosal antiviral IgA." The co-first authors of the study are Dr. Ji Eun Oh, Dr. Eric Song and Dr. Eric Song from Yale University. Dr. Miyu Moriyama.

The author writes that the mucosal surface is constantly exposed to various types of pathogens and toxins, while the mucosa contains its own immune defense system that can fight air or foodborne pathogens. "The mucosal barrier has several defense mechanisms, including innate defenses such as mucus, antimicrobial peptides, natural antibodies, and epithelial layers, as well as adaptive immune defenses involving various immune cells and effector mechanisms."

When challenged, these barrier tissues produce B cells, which in turn secrete immunoglobulin A antibodies. Unlike vaccines that trigger a system-wide immune response, IgA antibodies act locally on the mucosal surface of the nose, stomach, and lungs.

Although the protective effects of IgA-producing cells against enteric pathogens have been well established, Iwasaki's laboratory wanted to know whether triggering the IgA response might also produce local immune defense against respiratory viruses. "Secretory immunoglobulin A (IgA) is the main Ig isotype on the mucosal surface, and its epithelial cells express multimeric Ig receptors that can transport dimeric IgA to the lumen," the research team pointed out. "Although the role of IgA in the intestinal mucosa has been extensively studied, the type of cells responsible for secreting IgA to protect the host from pathogens in the lower respiratory tract is unclear."

Researchers at Yale University collaborated with researchers at the Icahn School of Medicine at Mount Sinai to test a protein-based vaccine designed to initiate an IgA immune response, which is injected into mice by injection, just like systemic immunity , Or inside the nose. Then, they exposed the mice to multiple strains of influenza virus.

They found that animals vaccinated intranasally were more resistant to respiratory flu than those vaccinated. A nasal vaccine, but not a systemic injection, also induces antibodies to protect animals from various influenza strains, not just against the strains that the vaccine is intended to prevent. "Our results show that local rather than systemic immunization with influenza virus induces the resident ASC in the lung mucosa to secrete IgA, which provides strong protection and cross-protection for the secondary attack of influenza virus."

Iwasaki said that although both vaccine injections and nasal vaccines increase the level of antibodies in the blood of mice, only nasal vaccines can secrete IgA into the lungs, and respiratory viruses need to infect the host in the lungs.

If nasal vaccines prove to be safe and effective for humans, Iwasaki hopes to combine them with vaccines and boosters that currently work on a system-wide basis to increase the strengthening of the immune system at the source of infection.

As the authors concluded, “In summary, our data shows that after intranasal immunization, IgA-producing cells form in the lungs and help protect against homologous and heterologous influenza virus infections. From our current The insights gained from the research may help design new vaccines against other respiratory viral infections."

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