Changes of urine metabolite profiles are induced by inactivated influenza vaccine inoculations in mice

Abstract

The safety evaluation of vaccines is critical to avoid the development of side effects in humans. To increase the sensitivity of detection for toxicity tests, it is important to capture not only pathological changes but also physiological changes. 1H nuclear magnetic resonance (NMR) spectroscopy analysis of biofluids produces profiles that show characteristic responses to changes in physiological status. In this study, mouse urine metabolomics analysis with 1H NMR was performed using different influenza vaccines of varying toxicity to assess the usefulness of 1H NMR in evaluating vaccine toxicity. Two types of influenza vaccines were used as model vaccines: a toxicity reference vaccine (RE) and a hemagglutinin split vaccine. According to the blood biochemical analyses, the plasma alanine transaminase levels were increased in RE-treated mice. Changes in metabolite levels between mice administered different types of influenza vaccines were observed in the 1H NMR spectra of urine, and a tendency toward dosage-dependent responses for some spectra was observed. Hierarchical clustering analyses and principal component analyses showed that the changes in various urine metabolite levels allowed for the classification of different types of vaccines. Among them, two liver-derived metabolites were shown to largely contribute to the formation of the cluster. These results demonstrate the possibility that urine metabolomics analysis could provide information about vaccine-induced toxicity and physiological changes.

Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines

“…Biomarker analysis using urine samples is also being applied in vaccine research. To evaluate the toxicity of two influenza vaccines with different toxicities in a mouse model, hydrogen-1 nuclear magnetic resonance spectroscopy was used to observe changes in urine metabolite levels, and findings were compared with existing toxicity indicators such as weight loss and leukopenia ( 194 ). In addition, analysis of changes in urinary cytokine levels, as a predictor of immunogenicity and reactogenicity, induced by the AS01 E -adjuvanted hepatitis B vaccine in healthy adults was used to evaluate the effectiveness of the vaccine (NCT01777295).…”

Gut Flora Mediated Mouse Metabolic Health Risk Caused by Dietary Exposure of Acetamiprid and Tebuconazole

“…IR and the disorder of carbohydrate metabolism occurred, indicating that many aspects of metabolism were affected. Serum biochemistry analysis is a commonly used method in investigating physiological changes, and it is an effective evidence in clinical diagnosis [20,21]. Pesticide exposure obviously led to a signi cant increase in serum cholesterol (Fig.…”

Serum NMR Profiling Reveals Differential Alterations in the Lipoproteome Induced by Pfizer-BioNTech Vaccine in COVID-19 Recovered Subjects and Naïve Subjects

“…1 H nuclear magnetic resonance (NMR) spectroscopy analysis of biofluids produces profiles that show characteristic responses to changes in physiological status and has been used in a few studies in the past to monitor changes in urinary metabolite levels in mice administered different types of influenza vaccines ( Sasaki et al, 2019 ) or to identify serum markers predictive of adverse reactions against smallpox ( McClenathan et al, 2017 ) as well as metabolic signatures of responses induced by a series of commonly used human vaccines, as reviewed in ( Diray-Arce et al, 2020 ). On the other hand, 1 H NMR has been also successfully used to monitor changes in metabolites and lipoproteins induced by SARS-CoV-2 infection ( Bruzzone et al, 2020 ; Kimhofer et al, 2020 ; Ballout et al, 2021 ; Baranovicova et al, 2021 ; Bizkarguenaga et al, 2021 ; Julkunen et al, 2021 ; Lodge et al, 2021 ; Masuda et al, 2021 ; Meoni et al, 2021 ).…”