2016
DOI: 10.4049/jimmunol.1600106
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Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination

Abstract: Effector T cells (TEFF) are a barrier to booster vaccination because they can rapidly kill Ag-bearing APCs before memory T cells are engaged. We report in this study that i.v. delivery of rhabdoviral vectors leads to direct infection of follicular B cells in the spleen, where the earliest evidence of secondary T cell responses was observed. This allows booster immunizations to rapidly expand CD8+ central memory T cells (TCM) during the acute phase of the primary response that is dominated by TEFF. Interestingl… Show more

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Cited by 39 publications
(58 citation statements)
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“…In preclinical murine studies splenic tropism of MG1-Maraba has been found to be fundamentally important to the mechanism by which MG1-Maraba potently boosts primed CD8 +  T-cell responses thus the detection of intrasplenic MG1-Maraba genomes in primates supports common mammalian bio-distribution properties. 31 Although genome was recovered from some tissues primarily comprising secondary lymphoid organs, no replicating virus was detected. This is consistent with the premise that the attenuated Maraba MG1 virus is extremely sensitive to type I IFN and selectively replicates in tumor cells that have defective type I responses but not in normal cells.…”
Section: Discussionmentioning
confidence: 99%
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“…In preclinical murine studies splenic tropism of MG1-Maraba has been found to be fundamentally important to the mechanism by which MG1-Maraba potently boosts primed CD8 +  T-cell responses thus the detection of intrasplenic MG1-Maraba genomes in primates supports common mammalian bio-distribution properties. 31 Although genome was recovered from some tissues primarily comprising secondary lymphoid organs, no replicating virus was detected. This is consistent with the premise that the attenuated Maraba MG1 virus is extremely sensitive to type I IFN and selectively replicates in tumor cells that have defective type I responses but not in normal cells.…”
Section: Discussionmentioning
confidence: 99%
“…This distribution supports the ability of MG1-MAGEA3 to directly boost T CM resulting in massive expansion of effector T-cells as previously elucidated in mice. 31 MG1-MAGEA3 was capable of inducing very large and specific anti-MAGE-A3 immunity comprising up to 13.47% of all circulating CD8 + T cells in primates.…”
Section: Discussionmentioning
confidence: 99%
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“…This was surprising as one might expect migratory antigen presenting cells to be killed prior to trafficking to secondary lymphoid organs and performing their antigen presenting functions if a primary response with effector T cells (T EFF ) targeting hDCT was still underway [92]. Subsequent mechanistic studies by Bridle et al [93] have shown that I.V. injection of VSV or Maraba MG1 in mice leads to direct infection of follicular B-cells in the spleen (Figure 3).…”
Section: Oncolytic Viruses In Cancer Vaccinationmentioning
confidence: 99%