PMID- 34811393
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221027
IS  - 2059-0105 (Electronic)
IS  - 2059-0105 (Linking)
VI  - 6
IP  - 1
DP  - 2021 Nov 22
TI  - Virus-based vaccine vectors with distinct replication mechanisms differentially 
      infect and activate dendritic cells.
PG  - 138
LID - 10.1038/s41541-021-00400-w [doi]
LID - 138
AB  - The precise mechanism by which many virus-based vectors activate immune responses 
      remains unknown. Dendritic cells (DCs) play key roles in priming T cell responses 
      and controlling virus replication, but their functions in generating protective 
      immunity following vaccination with viral vectors are not always well understood. 
      We hypothesized that highly immunogenic viral vectors with identical cell entry 
      pathways but unique replication mechanisms differentially infect and activate DCs 
      to promote antigen presentation and activation of distinctive antigen-specific T 
      cell responses. To evaluate differences in replication mechanisms, we utilized a 
      rhabdovirus vector (vesicular stomatitis virus; VSV) and an 
      alphavirus-rhabdovirus hybrid vector (virus-like vesicles; VLV), which replicates 
      like an alphavirus but enters the cell via the VSV glycoprotein. We found that 
      while virus replication promotes CD8(+) T cell activation by VLV, replication is 
      absolutely required for VSV-induced responses. DC subtypes were differentially 
      infected in vitro with VSV and VLV, and displayed differences in activation 
      following infection that were dependent on vector replication but were 
      independent of interferon receptor signaling. Additionally, the ability of the 
      alphavirus-based vector to generate functional CD8(+) T cells in the absence of 
      replication relied on cDC1 cells. These results highlight the differential 
      activation of DCs following infection with unique viral vectors and indicate 
      potentially discrete roles of DC subtypes in activating the immune response 
      following immunization with vectors that have distinct replication mechanisms.
CI  - (c) 2021. The Author(s).
FAU - Chiale, Carolina
AU  - Chiale C
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY, USA.
AD  - Division of Biological Sciences, University of California San Diego, 9500 Gilman 
      Drive, La Jolla, CA, 92093, USA.
FAU - Marchese, Anthony M
AU  - Marchese AM
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY, USA.
FAU - Furuya, Yoichi
AU  - Furuya Y
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY, USA.
FAU - Robek, Michael D
AU  - Robek MD
AUID- ORCID: 0000-0002-0709-4201
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY, USA. robekm@amc.edu.
LA  - eng
GR  - R01 AI124006/AI/NIAID NIH HHS/United States
GR  - R01AI124006/U.S. Department of Health & Human Services | NIH | National Institute 
      of Allergy and Infectious Diseases (NIAID)/
PT  - Journal Article
DEP - 20211122
PL  - England
TA  - NPJ Vaccines
JT  - NPJ vaccines
JID - 101699863
PMC - PMC8608815
COIS- M.D.R. reports financial relationships with CaroGen Corporation, which is seeking 
      to commercialize the VLV platform, and research funding from Gilead Sciences, 
      outside of this work. In addition, M.D.R. has received royalties from a patent 
      related to the VLV technology. The other authors declare no competing interests. 
      These entities played no role in the study design, interpretation of data, 
      writing the manuscript, or decision to publish.
EDAT- 2021/11/24 06:00
MHDA- 2021/11/24 06:01
PMCR- 2021/11/22
CRDT- 2021/11/23 06:08
PHST- 2020/11/22 00:00 [received]
PHST- 2021/10/22 00:00 [accepted]
PHST- 2021/11/23 06:08 [entrez]
PHST- 2021/11/24 06:00 [pubmed]
PHST- 2021/11/24 06:01 [medline]
PHST- 2021/11/22 00:00 [pmc-release]
AID - 10.1038/s41541-021-00400-w [pii]
AID - 400 [pii]
AID - 10.1038/s41541-021-00400-w [doi]
PST - epublish
SO  - NPJ Vaccines. 2021 Nov 22;6(1):138. doi: 10.1038/s41541-021-00400-w.