Journal article
Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine
The Journal of infectious diseases, Vol.229(3), pp.786-794
03/14/2024
DOI: 10.1093/infdis/jiad086
PMCID: PMC10938199
PMID: 36994927
Abstract
Live attenuated vaccines induce beneficial clinical outcomes, thought to be due to immune modulation. After yellow fever virus vaccination, we observed a reduction in T-cell receptor signaling. This may be a potential "off target" effect that influences clinical outcomes.
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.
Details
- Title: Subtitle
- Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine
- Creators
- J. Xiang - University of Iowa, Internal MedicineQ. Chang - Iowa City VA Health Care SystemJ. H. McLinden - University of Iowa, Internal MedicineN. Bhattarai - Center for Biologics Evaluation and ResearchJ. L. Welch - Iowa City VA Health Care SystemT. M. Kaufman - University of IowaJack T. Stapleton - University of Iowa, Infectious Diseases
- Resource Type
- Journal article
- Publication Details
- The Journal of infectious diseases, Vol.229(3), pp.786-794
- DOI
- 10.1093/infdis/jiad086
- PMID
- 36994927
- PMCID
- PMC10938199
- NLM abbreviation
- J Infect Dis
- ISSN
- 0022-1899
- eISSN
- 1537-6613
- Publisher
- Oxford Univ Press
- Number of pages
- 9
- Grant note
- University of Iowa Carver College of Medicine 5T32AI343 / National Institute of Allergy and Infectious Diseases, National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) BX000207 / U.S. Department of Veterans Affairs; US Department of Veterans Affairs
- Language
- English
- Electronic publication date
- 03/30/2023
- Date published
- 03/14/2024
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984473218102771
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