Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine
Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023..
BACKGROUND: Live attenuated vaccines alter immune functions and are associated with beneficial outcomes. We previously demonstrated that live attenuated yellow fever virus (YFV) vaccine (LA-YF-Vax) dampens T-cell receptor (TCR) signaling in vitro via an RNA-based mechanism. We examined study participants before and after LA-YF-Vax to assess TCR-mediated functions in vivo.
METHODS: Serum samples and peripheral blood mononuclear cells (PBMCs) were obtained before and after LA-YF-Vax (with or without additional vaccines) or quadrivalent influenza vaccine. TCR-mediated activation was determined by interleukin 2 release or phosphorylation of the lymphocyte-specific Src kinase. TCR-regulating phosphatase (protein tyrosine phosphatase receptor type E [PTPRE]) expression was also measured.
RESULTS: Compared with prevaccination findings, LA-YF-Vax recipient PBMCs demonstrated transient reduction in interleukin 2 release after TCR stimulation and PTPRE levels, unlike in control participants who received quadrivalent influenza vaccine. YFV was detected in 8 of 14 participants after LA-YF-Vax. After incubation of healthy donor PBMCs in serum-derived extracellular vesicles prepared from LA-YF-Vax recipients, TCR signaling and PTPRE levels were reduced after vaccination, even in participants without detectable YFV RNA.
CONCLUSIONS: LA-YF-Vax reduces TCR functions and PTPRE levels after vaccination. Extracellular vesicles from serum recapitulated this effect in healthy cells. This likely contributes to the reduced immunogenicity for heterologous vaccines after LA-YF-Vax administration. Identification of specific immune mechanisms related to vaccines should contribute to understanding of the "off-target," beneficial effects of live vaccines.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:229 |
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| Enthalten in: |
The Journal of infectious diseases - 229(2024), 3 vom: 14. März, Seite 786-794 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiang, J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 16.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/infdis/jiad086 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM354998579 |
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| 100 | 1 | |a Xiang, J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023. | ||
| 520 | |a BACKGROUND: Live attenuated vaccines alter immune functions and are associated with beneficial outcomes. We previously demonstrated that live attenuated yellow fever virus (YFV) vaccine (LA-YF-Vax) dampens T-cell receptor (TCR) signaling in vitro via an RNA-based mechanism. We examined study participants before and after LA-YF-Vax to assess TCR-mediated functions in vivo | ||
| 520 | |a METHODS: Serum samples and peripheral blood mononuclear cells (PBMCs) were obtained before and after LA-YF-Vax (with or without additional vaccines) or quadrivalent influenza vaccine. TCR-mediated activation was determined by interleukin 2 release or phosphorylation of the lymphocyte-specific Src kinase. TCR-regulating phosphatase (protein tyrosine phosphatase receptor type E [PTPRE]) expression was also measured | ||
| 520 | |a RESULTS: Compared with prevaccination findings, LA-YF-Vax recipient PBMCs demonstrated transient reduction in interleukin 2 release after TCR stimulation and PTPRE levels, unlike in control participants who received quadrivalent influenza vaccine. YFV was detected in 8 of 14 participants after LA-YF-Vax. After incubation of healthy donor PBMCs in serum-derived extracellular vesicles prepared from LA-YF-Vax recipients, TCR signaling and PTPRE levels were reduced after vaccination, even in participants without detectable YFV RNA | ||
| 520 | |a CONCLUSIONS: LA-YF-Vax reduces TCR functions and PTPRE levels after vaccination. Extracellular vesicles from serum recapitulated this effect in healthy cells. This likely contributes to the reduced immunogenicity for heterologous vaccines after LA-YF-Vax administration. Identification of specific immune mechanisms related to vaccines should contribute to understanding of the "off-target," beneficial effects of live vaccines | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Off-target vaccine effects | |
| 650 | 4 | |a PTPRE | |
| 650 | 4 | |a T lymphocyte | |
| 650 | 4 | |a T-cell receptor | |
| 650 | 4 | |a live attenuated yellow fever vaccine | |
| 650 | 4 | |a vaccine | |
| 650 | 4 | |a yellow fever virus | |
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| 650 | 7 | |a Interleukin-2 |2 NLM | |
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| 650 | 7 | |a Vaccines, Combined |2 NLM | |
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| 650 | 7 | |a RNA |2 NLM | |
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| 650 | 7 | |a Vaccines, Attenuated |2 NLM | |
| 700 | 1 | |a Chang, Q |e verfasserin |4 aut | |
| 700 | 1 | |a McLinden, J H |e verfasserin |4 aut | |
| 700 | 1 | |a Bhattarai, N |e verfasserin |4 aut | |
| 700 | 1 | |a Welch, J L |e verfasserin |4 aut | |
| 700 | 1 | |a Kaufman, T M |e verfasserin |4 aut | |
| 700 | 1 | |a Stapleton, Jack T |e verfasserin |4 aut | |
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