ArticlePLoS pathogens2016
Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 72 citations in OpenAlex.
- Cancer viroimmunotherapy platforms based on varicella-zoster virus and cytomegalovirus.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- MAPKAP Kinase 2 Orchestrates Memory T Cell Inflation in Cytomegalovirus Infection.bioRxiv : the preprint server for biology · 2026Article
- Leukotriene B4 regulates T cell recognition and control of MCMV in mucosal tissues.Mucosal immunology · 2025Article
- A versatile silica nanoparticle platform for induction of T cell responses - applied for therapeutic vaccination against HPV16 E6/E7-positive tumors in MHC-humanized mice.Oncoimmunology · 2025Article
- A safe, T cell-inducing heterologous vaccine against elephant endotheliotropic herpesvirus in a proof-of-concept study.Nature communications · 2025Article
- Defining molecular circuits of CD8+ T cell responses in tissues during latent viral infection.The Journal of experimental medicine · 2025Article
- Recent thymic emigrants preferentially undergo memory inflation after persistent infection.PLoS pathogens · 2025Article
- Advances in viral vector-based delivery systems for gene therapy: a comprehensive review.3 Biotech · 2025Review
- Exploitation of Unconventional CD8 T-Cell Responses Induced by Engineered Cytomegaloviruses for the Development of an HIV-1 Vaccine.Vaccines · 2025Review
- Memory inflation: Beyond the acute phase of viral infection.Cell proliferation · 2024Review
- Transcriptional signature of durable effector T cells elicited by a replication defective HCMV vaccine.NPJ vaccines · 2024Article
- NFAT signaling is indispensable for persistent memory responses of MCMV-specific CD8+ T cells.PLoS pathogens · 2024Article
- Dynamic monitoring of viral gene expression reveals rapid antiviral effects of CD8 T cells recognizing the HCMV-pp65 antigen.Frontiers in immunology · 2024Article
- Modulation of cytomegalovirus immune evasion identifies direct antigen presentation as the predominant mode of CD8 T-cell priming during immune reconstitution after hematopoietic cell transplantation.Frontiers in immunology · 2024Article
- Article
- 'Stem-like' precursors are the fount to sustain persistent CD8Nature immunology · 2022Review
- MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination.Cellular & molecular immunology · 2022Article
- Targeted T cell receptor gene editing provides predictable T cell product function for immunotherapy.Cell reports. Medicine · 2021Article
- Enhancing proteasomal processing improves survival for a peptide vaccine used to treat glioblastoma.Science translational medicine · 2021Article
- Direct Evidence for Viral Antigen Presentation during Latent Cytomegalovirus Infection.Pathogens (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 5 countries.
Funding
Abstract
Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGIRNASFI to dissect this phenomenon at the molecular level. A recombinant MCMV expressing HGIRNASFI on the C-terminus of M45, in contrast to wild-type MCMV, enabled peptide processing by the constitutive proteasome, direct antigen presentation, and an inflation of antigen-specific effector memory cells. Consequently, our results indicate that constitutive proteasome processing of antigenic epitopes in latently infected cells is required for robust inflationary responses. This insight allows utilizing the epitope positioning in the design of CMV-based vectors as a novel strategy for enhancing their efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.