Establishment of isotype-switched, antigen-specific B cells in multiple mucosal tissues using non-mucosal immunization

Abstract

Although most pathogens infect the human body via mucosal surfaces, very few injectable vaccines can specifically target immune cells to these tissues where their effector functions would be most desirable. We have previously shown that certain adjuvants can program vaccine-specific helper T cells to migrate to the gut, even when the vaccine is delivered non-mucosally. It is not known whether this is true for antigen-specific B cell responses. Here we show that a single intradermal vaccination with the adjuvant double mutant heat-labile toxin (dmLT) induces a robust endogenous, vaccine-specific, isotype-switched B cell response. When the vaccine was intradermally boosted, we detected non-circulating vaccine-specific B cell responses in the lamina propria of the large intestines, Peyer’s patches, and lungs. When compared to the TLR9 ligand adjuvant CpG, only dmLT was able to drive the establishment of isotype-switched resident B cells in these mucosal tissues, even when the dmLT-adjuvanted vaccine was administered non-mucosally. Further, we found that the transcription factor Batf3 was important for the full germinal center reaction, isotype switching, and Peyer’s patch migration of these B cells. Collectively, these data indicate that specific adjuvants can promote mucosal homing and the establishment of activated, antigen-specific B cells in mucosal tissues, even when these adjuvants are delivered by a non-mucosal route. These findings could fundamentally change the way future vaccines are formulated and delivered.

Current vaccine strategies and novel approaches to combatting Francisella infection

“…This is particularly true in the case of adjuvants that can target mucosal tissues with appropriate immune responses. For example, it is known that the ADP-ribosylating adjuvant double mutant heat labile toxin (dmLT) can drive both antigen specific T and B cells into mucosal tissues such as the lung and gut [ 101 , 102 ]. This is true even when the dmLT adjuvanted vaccine was delivered non-mucosally.…”