Clarification of how secretory IgA antibodies, produced in the nasal mucosa through intranasal immunization, inhibit viral infection at the monoclonal antibody level.
Subcutaneous and intramuscular injectable vaccines have proven to be highly effective in preventing severe disease caused by viral infections by inducing IgG antibodies in the bloodstream. However, these vaccines often fail to stimulate the production of secretory IgA antibodies in the upper respiratory tract, the primary entry point for viruses such as influenza and new coronaviruses. As a result, there has been a growing focus on developing intranasal vaccines that can trigger the production of antigen-specific secretory IgA antibodies in the nasal mucosa. While the effectiveness of intranasal vaccines has been assessed through the analysis of nasal washes containing a variety of antibodies, a thorough investigation of the specific antibody populations at the monoclonal level is needed.
We have developed a method for rapidly producing many antigen-specific monoclonal IgA antibodies. Using this technique, we have successfully isolated 99 monoclonal IgA clones from nasal mucosa and 114 monoclonal IgA or IgG clones from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. DNA sequence analysis of these antibody clones showed that the B cells activated by nasal challenges were the primary precursors of antigen-specific plasma cells in the spleen, lungs, and blood, potentially contributing to antibody production in the lower respiratory tract and systemic circulation.
We also showed that even monomeric IgA antibodies that do not exhibit virus-neutralizing activity by themselves can induce such activity when converted to secretory IgA antibodies. This occurs because secretory IgA antibodies possess four to eight antigen-binding sites, enhancing their effectiveness against viruses that monomeric antibodies—with only two binding sites—can not adequately neutralize. Additionally, administering secretory IgA antibodies to hamsters as a preventive measure was found to reduce weight loss caused by infection with SARS-CoV-2 virus.
The results highlight a unique mechanism of action associated with intranasal vaccines, which is not present in conventional injectable vaccines. These findings offer valuable insights into the workings of intranasal vaccines and are anticipated to contribute to the development of new preventive agents for infections that utilize secretory IgA antibodies.
Intranasal immunization triggers secretory IgA antibodies ( ) in the nasal mucosa and monomeric IgA antibodies ( 
) in the blood. Both are produced by plasma cells (? and ? ) from common antibody-producing cells (??) activated by nasal antigens. While monomeric IgA generally lacks virus-neutralizing activity, secretory IgA is highly effective at neutralizing viruses and preventing infections in the nasal mucosa.
Original article information
Title
Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein
Authors
Kentarou Waki, Hideki Tani, Yumiko Saga, Takahisa Shimada, Emiko Yamazaki, Seiichi Koike, Okada Mana, Masaharu Isobe, Nobuyuki Kurosawa
Published in
elife