Evaluation of marker gene expression as a potential predictive marker of leukopenic toxicity for inactivated influenza vaccines

Momose, Haruka; Hiradate, Yuki; Furuhata, Keiko; Takai, Mamiko; Kamachi, Kazunari; Asanuma, Hideki; Ishii, Ken J.; Mizukami, Tamio; Hamaguchi, Isao

doi:10.1016/j.biologicals.2017.08.003

Cited by 6 publications

(20 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Functionally, these biomarker genes tend to correlate with the white blood cell (WBC) count in the peripheral blood of animals (leukopenic toxicity) that were treated with the inactivated influenza vaccine [31,32]. It has been known that intraperitoneal injection of the WPV causes leukopenic toxicity in mice, and this bioactivity has been used as an index for the safety evaluation of inactivated influenza vaccines in Japan, which is termed the LTT [19].…”

Section: Ngfrmentioning

confidence: 99%

“…This strategy will reduce the number of animals required and shorten the testing duration. We tried to identify the genes useful for the prediction of the WBC count from the biomarker gene set by multiple linear regression analysis and a stepwise method [32]. In the multiple regression analysis method, a linear equation expressed by the following formula was derived, and a predicted value was calculated.…”

Section: Development Of An Alternative Assay For the Leukopenic Toxicmentioning

confidence: 99%

“…Predicted leukocyte numbers produced by these models can predict leukopenia caused by WPVs with high accuracy (Figure 1). Even if the predicted values of individuals are analyzed, the deviation between the predicted value and the measured value is small [32]. In addition, variations in the WBC count owing to individual differences are reproduced with high accuracy [32].…”

Section: Development Of An Alternative Assay For the Leukopenic Toxicmentioning

confidence: 99%

“…Even if the predicted values of individuals are analyzed, the deviation between the predicted value and the measured value is small [32]. In addition, variations in the WBC count owing to individual differences are reproduced with high accuracy [32]. Therefore, it was shown that the leukopenic activity can be predicted by means of the identified marker gene set.…”

Section: Development Of An Alternative Assay For the Leukopenic Toxicmentioning

confidence: 99%

“…Leukopenic activity is also present in compounds with an excellent adjuvant activity such as Poly I:C and R848 [43]. Therefore, we analyzed the CpG K3 adjuvant, which manifested a slight leukopenic activity according to the newly developed multiple regression Equation [32]. As a result, a slight leukopenic activity was observed in animals that received the CpG K3 adjuvant in combination with the SV.…”

Section: Development Of An Alternative Assay For the Leukopenic Toxicmentioning

confidence: 99%

See 4 more Smart Citations

Genomic Approaches Enable Evaluation of the Safety and Quality of Influenza Vaccines and Adjuvants

Mizukami¹,

Hamaguchi²

2018

Influenza - Therapeutics and Challenges

Self Cite

View full text Add to dashboard Cite

Vaccination is an effective means for prevention of the progression and spread of influenza virus infection. Nonetheless, there is a risk of adverse reactions, such as pain and fever, during the vaccination. In addition, because people from a wide age range, that is, from children to the elderly, are inoculated with vaccines, safety confirmation of these vaccines is important. Safety assessments of a vaccine, in the form of quality controls, have been carried out on animals. For example, the abnormal toxicity test is based on body weight changes as a toxicity index, and the leukopenic toxicity test can evaluate hematological toxicity. Meanwhile, since the 2000s, safety evaluation of drugs and chemicals by the genomic approach has been conducted frequently. The benefits with respect to safety evaluation are high sensitivity and abundant information about toxicity profiles. In this chapter, we describe the genes that are helpful as safety assessment markers and their usefulness for safety testing and vaccine development. In addition, this information may provide toxicity profiles, help understand the reactogenicity of nasal vaccines or adjuvants, and explain the prospects of genomic analyses in the development of novel vaccines and adjuvants.

show abstract

Section: Ngfrmentioning

confidence: 99%

Section: Development Of An Alternative Assay For the Leukopenic Toxicmentioning

confidence: 99%

Section: Development Of An Alternative Assay For the Leukopenic Toxicmentioning

confidence: 99%

Section: Development Of An Alternative Assay For the Leukopenic Toxicmentioning

confidence: 99%

Section: Development Of An Alternative Assay For the Leukopenic Toxicmentioning

confidence: 99%

See 3 more Smart Citations

Genomic Approaches Enable Evaluation of the Safety and Quality of Influenza Vaccines and Adjuvants

Mizukami¹,

Hamaguchi²

2018

Influenza - Therapeutics and Challenges

Self Cite

View full text Add to dashboard Cite

show abstract

Establishment of a novel safety assessment method for vaccine adjuvant development

Momose

Hiradate

Mizukami

et al. 2018

Vaccine

View full text Add to dashboard Cite

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

Kusunoki

Momose

Furuhata

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Evaluation of marker gene expression as a potential predictive marker of leukopenic toxicity for inactivated influenza vaccines

Cited by 6 publications

References 12 publications

Genomic Approaches Enable Evaluation of the Safety and Quality of Influenza Vaccines and Adjuvants

Genomic Approaches Enable Evaluation of the Safety and Quality of Influenza Vaccines and Adjuvants

Establishment of a novel safety assessment method for vaccine adjuvant development

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

Contact Info

Product

Resources

About