Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice.

Autor:	Poston TB; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: taylor_poston@med.unc.edu., Girardi J; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Polson AG; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Bhardwaj A; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Yount KS; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Jaras Salas I; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Trim LK; Center for Immunology and Infection Control and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia., Li Y; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., O'Connell CM; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Leahy D; Center for Immunology and Infection Control and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia., Harris JM; Center for Immunology and Infection Control and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia., Beagley KW; Center for Immunology and Infection Control and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia., Goonetilleke N; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Darville T; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jazyk:	angličtina
Zdroj:	Mucosal immunology [Mucosal Immunol] 2024 Oct; Vol. 17 (5), pp. 1005-1018. Date of Electronic Publication: 2024 Jul 03.
DOI:	10.1016/j.mucimm.2024.06.012
Abstrakt:	A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient Chlamydia muridarum CM972 and elicit protection in naïve mice. MVA.OmcB or MVA.CPAF increased antigen-specific T cells in CM972-immune mice ∼150 and 50-fold, respectively, but failed to improve bacterial clearance. ChAd.OmcB/MVA.OmcB prime-boost immunization of naïve mice elicited a cluster of differentiation (CD) 8-dominant T-cell response dominated by cluster of differentiation (CD)8 T cells that failed to protect. ChAd.CPAF/ChAd.CPAF prime-boost also induced a CD8-dominant response with a marginal reduction in burden. Challenge of ChAd.CPAF-immunized mice genetically deficient in CD4 or CD8 T cells showed that protection was entirely CD4-dependent. CD4-deficient mice had prolonged infection, whereas CD8-deficient mice had higher frequencies of CPAF-specific CD4 T cells, earlier clearance, and reduced burden than wild-type controls. These data reinforce the essential nature of the CD4 T-cell response in protection from chlamydial genital infection in mice and the need for vaccine platforms that drive CD4-dominant responses. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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