Presenting Author: Michael J Johnson
, Research Associate at Univ. of Colorado Anschutz Med. Campus
Abstract:
Development of trained immunity after vaccination is of growing interest. We studied innate immune responses to RZV, which is a highly efficacious adjuvanted recombinant glycoprotein E (rgE) zoster vaccine administered in 2 doses.
Blood mononuclear cells from 10 RZV recipients were stimulated with gE overlapping peptides, rgE or medium. B cell, monocyte and DC responses were measured by PDL1 expression and NK, γδ, and conventional T cell (Tconv) responses by CD25 and CD137 co-expression. Innate and Tconv responses had similar 2-phase kinetics with a transient increase post-dose 1 and persistent increase post-dose 2 for up to 1year. In 14 vaccinees, we verified that DC, NK and monocyte responses to rgE remained higher than pre-vaccination for up to 5 years. Innate and Tconv responses did not correlate with each other ruling out bystander activation. Purified monocytes and NK cells from 10 vaccinees (6 CMV-seropositive) stimulated with rgE, CMV lysate or medium showed increased responses to both rgE and CMV from pre to postvaccination indicating the development of homologous and heterologous trained immunity. Monocyte ATAC-seq analysis showed significant chromatin changes in 16 genes from pre to postvaccination, including decreased chromatin accessibility of the TGFβ pathway postvaccination, which may represent the mechanism underlying the development of trained immunity.
In conclusion, RZV generated robust and lasting trained immunity that may contribute to its high efficacy.
Trained Immunity Generated by The Recombinant Zoster Vaccine (RZV)
Category
Poster and Podium (Block Symposium)
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Date: May 6 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1