Identification of Biomarkers of Vaccine Reactogenicity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA494386 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Systems vaccinology approaches have been used to successfully define early signatures of the vaccine-induced immune response. However, the possibility that transcriptomics can also predict vaccine reactogenicity has not been fully explored. We have compared four licensed vaccines that have a demonstrated safety profile, as well as three agonists of TLRs that have a known inflammatory potential, to elucidate the transcriptomic profile of an acceptable response to a vaccination versus those which push the inflammatory envelope. In mice, we looked at the transcriptomic changes in the injected muscle, the lymph node that drained the muscle and the PBMC isolated from the circulating blood from the very early timepoint of 4 hours to over the period of one week. A detailed examination and comparative analysis of the transcriptome from each of these tissues, at all the timepoints of 4, 8, 24, 48, 72 and 168 hr and with these eight different vaccines, TLR or saline control injections, revealed a set of novel biomarkers that are reflective of inflammation after vaccination. These biomarkers are easily sampled and readily measurable in the peripheral blood, providing a useful tool to predict levels of reactogenicity, as a way to select candidates with acceptable immunogenicity and safety profiles.
2019-01-31 | GSE120661 | GEO
Project description:The local and systemic symptoms that follow vaccination -collectively referred to as reactogenicity- are common, yet the mechanisms underlying individual variability remain poorly understood. Through longitudinal immune profiling of vaccinated individuals and mechanistic studies in mice, we identified key immunological determinants of reactogenicity induced by mRNA vaccines. Systemic adverse events were associated with stronger interferon and pro-inflammatory responses following the second dose of COVID-19 vaccine, which were also correlated with the magnitude of the antigen-specific adaptive responses. This heightened inflammation occurred within 24 hours of vaccination and originated primarily from the injection site and was characterized by enhanced recruitment and activation of myeloid cells, particularly monocytes. Two mechanisms contributed to this response: (1) early interferon production by muscle T cells generated after the first dose and (2) FcγR-dependent chemokine induction by antigen-specific antibodies. Consistently, serum antibody levels prior to vaccination correlated positively with reactogenicity. In addition to this local amplification mechanism, variability in reactogenicity was influenced by the baseline immune state, as individuals with a pre-existing interferon-stimulated gene signature in monocytes, detectable at both transcriptomic and epigenetic levels, were more prone to systemic symptoms. Our findings reveal molecular and cellular mechanisms driving vaccine reactogenicity, providing a framework for the design of less reactogenic vaccines.
2026-06-05 | GSE333952 | GEO
Project description:The local and systemic symptoms that follow vaccination -collectively referred to as reactogenicity- are common, yet the mechanisms underlying individual variability remain poorly understood. Through longitudinal immune profiling of vaccinated individuals and mechanistic studies in mice, we identified key immunological determinants of reactogenicity induced by mRNA vaccines. Systemic adverse events were associated with stronger interferon and pro-inflammatory responses following the second dose of COVID-19 vaccine, which were also correlated with the magnitude of the antigen-specific adaptive responses. This heightened inflammation occurred within 24 hours of vaccination and originated primarily from the injection site and was characterized by enhanced recruitment and activation of myeloid cells, particularly monocytes. Two mechanisms contributed to this response: (1) early interferon production by muscle T cells generated after the first dose and (2) FcγR-dependent chemokine induction by antigen-specific antibodies. Consistently, serum antibody levels prior to vaccination correlated positively with reactogenicity. In addition to this local amplification mechanism, variability in reactogenicity was influenced by the baseline immune state, as individuals with a pre-existing interferon-stimulated gene signature in monocytes, detectable at both transcriptomic and epigenetic levels, were more prone to systemic symptoms. Our findings reveal molecular and cellular mechanisms driving vaccine reactogenicity, providing a framework for the design of less reactogenic vaccines.
2026-05-26 | GSE332761 | GEO
Project description:The local and systemic symptoms that follow vaccination -collectively referred to as reactogenicity- are common, yet the mechanisms underlying individual variability remain poorly understood. Through longitudinal immune profiling of vaccinated individuals and mechanistic studies in mice, we identified key immunological determinants of reactogenicity induced by mRNA vaccines. Systemic adverse events were associated with stronger interferon and pro-inflammatory responses following the second dose of COVID-19 vaccine, which were also correlated with the magnitude of the antigen-specific adaptive responses. This heightened inflammation occurred within 24 hours of vaccination and originated primarily from the injection site and was characterized by enhanced recruitment and activation of myeloid cells, particularly monocytes. Two mechanisms contributed to this response: (1) early interferon production by muscle T cells generated after the first dose and (2) FcγR-dependent chemokine induction by antigen-specific antibodies. Consistently, serum antibody levels prior to vaccination correlated positively with reactogenicity. In addition to this local amplification mechanism, variability in reactogenicity was influenced by the baseline immune state, as individuals with a pre-existing interferon-stimulated gene signature in monocytes, detectable at both transcriptomic and epigenetic levels, were more prone to systemic symptoms. Our findings reveal molecular and cellular mechanisms driving vaccine reactogenicity, providing a framework for the design of less reactogenic vaccines.
2026-05-27 | GSE332923 | GEO
Project description:The local and systemic symptoms that follow vaccination -collectively referred to as reactogenicity- are common, yet the mechanisms underlying individual variability remain poorly understood. Through longitudinal immune profiling of vaccinated individuals and mechanistic studies in mice, we identified key immunological determinants of reactogenicity induced by mRNA vaccines. Systemic adverse events were associated with stronger interferon and pro-inflammatory responses following the second dose of COVID-19 vaccine, which were also correlated with the magnitude of the antigen-specific adaptive responses. This heightened inflammation occurred within 24 hours of vaccination and originated primarily from the injection site and was characterized by enhanced recruitment and activation of myeloid cells, particularly monocytes. Two mechanisms contributed to this response: (1) early interferon production by muscle T cells generated after the first dose and (2) FcγR-dependent chemokine induction by antigen-specific antibodies. Consistently, serum antibody levels prior to vaccination correlated positively with reactogenicity. In addition to this local amplification mechanism, variability in reactogenicity was influenced by the baseline immune state, as individuals with a pre-existing interferon-stimulated gene signature in monocytes, detectable at both transcriptomic and epigenetic levels, were more prone to systemic symptoms. Our findings reveal molecular and cellular mechanisms driving vaccine reactogenicity, providing a framework for the design of less reactogenic vaccines.
2026-06-05 | GSE333235 | GEO
Project description:The local and systemic symptoms that follow vaccination -collectively referred to as reactogenicity- are common, yet the mechanisms underlying individual variability remain poorly understood. Through longitudinal immune profiling of vaccinated individuals and mechanistic studies in mice, we identified key immunological determinants of reactogenicity induced by mRNA vaccines. Systemic adverse events were associated with stronger interferon and pro-inflammatory responses following the second dose of COVID-19 vaccine, which were also correlated with the magnitude of the antigen-specific adaptive responses. This heightened inflammation occurred within 24 hours of vaccination and originated primarily from the injection site and was characterized by enhanced recruitment and activation of myeloid cells, particularly monocytes. Two mechanisms contributed to this response: (1) early interferon production by muscle T cells generated after the first dose and (2) FcγR-dependent chemokine induction by antigen-specific antibodies. Consistently, serum antibody levels prior to vaccination correlated positively with reactogenicity. In addition to this local amplification mechanism, variability in reactogenicity was influenced by the baseline immune state, as individuals with a pre-existing interferon-stimulated gene signature in monocytes, detectable at both transcriptomic and epigenetic levels, were more prone to systemic symptoms. Our findings reveal molecular and cellular mechanisms driving vaccine reactogenicity, providing a framework for the design of less reactogenic vaccines.
2026-06-05 | GSE333510 | GEO
Project description:Biomarkers for canine Leptospira vaccine potency
| PRJNA793869 | ENA
Project description:Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses, with reactogenicity influencing their use during and beyond the COVID-19 pandemic. However, despite the clinical significance, the underpinning mechanisms remain unclear. Innate and innate-like lymphocytes, such as mucosal-associated invariant T cells, are highly sensitive to cytokines and can enhance both innate and adaptive vaccine responses. We compared longitudinal human immune responses and reactogenicity following homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination to define the interactions between innate-like lymphocytes and adaptive immunity – and their in vivo consequences. Specifically, Ad vector priming elicited robust early type I interferon (IFN)-mediated activation of innate-like T cells, augmenting T cell responses (innate to adaptive signalling), which diminished upon boosting in the presence of anti-vector immunity. In contrast, mRNA vaccine responses in innate-like cells were markedly enhanced after boosting. This was initiated by IFN-γ signalling from spike-specific memory T cells and amplified by IFN-γR+ innate-like lymphocyte networks (adaptive to innate signalling). Importantly, extending the interval between doses reduced inflammatory responses to mRNA vaccination. In an independent clinical trial, spike-specific T cells predicted severe reactogenicity to mRNA vaccine boosting regardless of the dosing interval and vaccine type. These findings reveal a close integration of innate-like and adaptive responses to novel vaccines, including an IFN-γ-mediated function of innate-like T cells in orchestrating critical early responses to mRNA vaccines which may have significant implications for optimising future vaccine regimens.
2025-08-29 | GSE304583 | GEO
Project description:Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses, with reactogenicity influencing their use during and beyond the COVID-19 pandemic. However, despite the clinical significance, the underpinning mechanisms remain unclear. Innate and innate-like lymphocytes, such as mucosal-associated invariant T cells, are highly sensitive to cytokines and can enhance both innate and adaptive vaccine responses. We compared longitudinal human immune responses and reactogenicity following homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination to define the interactions between innate-like lymphocytes and adaptive immunity – and their in vivo consequences. Specifically, Ad vector priming elicited robust early type I interferon (IFN)-mediated activation of innate-like T cells, augmenting T cell responses (innate to adaptive signalling), which diminished upon boosting in the presence of anti-vector immunity. In contrast, mRNA vaccine responses in innate-like cells were markedly enhanced after boosting. This was initiated by IFN-γ signalling from spike-specific memory T cells and amplified by IFN-γR+ innate-like lymphocyte networks (adaptive to innate signalling). Importantly, extending the interval between doses reduced inflammatory responses to mRNA vaccination. In an independent clinical trial, spike-specific T cells predicted severe reactogenicity to mRNA vaccine boosting regardless of the dosing interval and vaccine type. These findings reveal a close integration of innate-like and adaptive responses to novel vaccines, including an IFN-γ-mediated function of innate-like T cells in orchestrating critical early responses to mRNA vaccines which may have significant implications for optimising future vaccine regimens.
2025-08-29 | GSE304584 | GEO
Project description:BioVacSafe (Biomarkers for enhanced vaccine immunosafety) Influenza challenge
| PRJNA732702 | ENA