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Int Immunol . Subcutaneous immunization with zymosan generates mucosal IgA-eliciting memory and protects mice from heterologous influenza virus inf

tetano

Editor, Senior Moderator
Int Immunol


. 2023 May 4;dxad013.
doi: 10.1093/intimm/dxad013. Online ahead of print. Subcutaneous immunization with zymosan generates mucosal IgA-eliciting memory and protects mice from heterologous influenza virus infection

Yoshihito Nihei[SUP] 1 2 [/SUP], Mizuki Higashiyama[SUP] 2 [/SUP], Kosuke Miyauchi[SUP] 3 [/SUP], Kei Haniuda[SUP] 2 [/SUP], Yusuke Suzuki[SUP] 1 [/SUP], Masato Kubo[SUP] 3 4 [/SUP], Daisuke Kitamura[SUP] 2 [/SUP]



Affiliations
Abstract

IgA is the most abundant isotype of antibodies and provides a first line of defense at the mucosa against pathogens invading the host. It has been widely accepted that the mucosal IgA response provided by vaccination requires mucosal inoculation, and intranasal inoculation has been proposed for vaccines against influenza virus. Considering the difficulty of intranasal vaccination in infants or elderly people, however, parenteral vaccination that provides the mucosal IgA response is desirable. Here, we demonstrate that subcutaneous immunization with zymosan, a yeast cell wall constituent known to be recognized by Dectin-1 and TLR2, potentiates the production of antigen-specific IgA antibodies in the sera and airway mucosa upon intranasal antigen challenge. We confirmed that the antigen-specific IgA-secreting cells accumulated in the lung and nasal-associated lymphoid tissues after the antigen challenge. Such an adjuvant effect of zymosan in the primary immunization for the IgA response depended on Dectin-1 signaling, but not on TLR2. The IgA response to the antigen challenge required both antigen-specific memory B and T cells, and the generation of memory T cells, but not memory B cells, depended on zymosan as an adjuvant. Finally, we demonstrated that subcutaneous inoculation of inactivated influenza virus with zymosan, but not with alum, mostly protected the mice from infection with a lethal dose of a heterologous virus strain. These data suggest that zymosan is a possible adjuvant for parenteral immunization that generates memory IgA responses to respiratory viruses such as influenza virus.

Keywords: Adjuvant; Dectin-1; airway mucosa; memory B cell.

 
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