Presenting Author: Ebony N Gary
, Postdoctoral fellow at Wistar Inst.
Abstract:
Many pathogens enter the host at mucosal sites. Peripheral vaccination supports robust antigen-specific cellular and humoral immunity but it requires active infection to pull antigen-specific memory cells to the mucosa and relies on passive transudation of antibodies to mucosal surfaces. We reported that co-delivery of the mucosal homing chemokine CCL27 (CTACK) with a DNA plasmid encoding parental SARS-CoV-2 spike (pS) generates antigen-specific IgA in the lung, antigen-specific CD8+ T cells at mucosal surfaces, and was 100% protective in a heterologous Delta VOC challenge model. Here, we extend this work and demonstrate that co-delivery of plasmid-encoded CTACK (+pCTACK) with pS supports protection from heterologous challenge with SARS-CoV-Omicron variants. pCTACK co-delivery significantly lowered viral loads when mice were challenged with Omicron variants BA.2 and XBB.1.5. In the context of Influenza HA DNA vaccination, co-delivery of pCTACK increased HA-specific antibodies in bronchoalveolar lavage, increased antigen-specific CD8+T cells in the lung mucosa, and altered challenge outcomes in vivo. These data have broad implications for the generation of mucosal immunity with parenteral vaccination and support the use of CCL27 to augment parenteral vaccine-induced immunity at mucosal surfaces and support improved outcomes following respiratory virus infection.
Plasmid-encoded CCL27 co-delivery enhances heterologous protection from respiratory virus challenge
Category
Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 05:00 PM to 05:15 PM Room: Room W175