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Updated: May 25, 2026
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
A need for careful evaluation of endotoxin contents in acellular pertussis-based combination vaccines
Michiyo Kataoka1, Masaki Ochiai, Akihiko Yamamoto
1Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
Abstract:
Two batches each of diphtheria-tetanus-acellular pertussis vaccine (DTaP) and that combined with inactivated polio vaccine purchased from foreign markets were tested by mouse body weight decreasing (BWD) toxicity test and Limulus amaebocyte lysate (LAL) test. Three out of the four imported vaccine batches showed the levels of BWD toxicity even comparable to that of DT-whole cell pertussis vaccine. BWD toxicity test is based on endotoxin dose-dependent weight loss of mice and has been used for controlling endotoxin in DTaP. Although of the strong BWD toxicity of the imported vaccines, there was no marked difference in LAL test results between the imported vaccines and Japanese DTaP. However, one imported DTaP batch showed very strong interference with LAL activity of spiked lipopolysaccharide (LPS). The batch interfered not only with LAL activity but also with pyrogenicity and prostaglandin E(2) induction activity. However, the pyrogenicity of the spiked LPS could be recovered from the precipitated fraction of the batch by treating with phosphate buffer to suggest the possibility of recovering in vivo toxicity. As an adequate in vitro test method could not be identified for controlling the safety of the interfering batch, an appropriate in vivo test would be required for testing such vaccines.
Insights
Foreign DTaP vaccines showed significant mouse body weight decreasing toxicity, comparable to older whole-cell pertussis vaccines. Standard Limulus amaebocyte lysate tests did not fully detect this toxicity, suggesting a need for in vivo testing for vaccine safety.
Area of Science:
- Vaccinology
- Toxicology
- Immunology
Background:
- Diphtheria-tetanus-acellular pertussis (DTaP) vaccines are crucial for public health.
- Controlling endotoxin levels in DTaP is essential for vaccine safety.
- Existing in vitro tests may not fully assess the safety of all vaccine formulations.
Purpose of the Study:
- To evaluate the toxicity of imported DTaP vaccines using mouse body weight decreasing (BWD) and Limulus amaebocyte lysate (LAL) tests.
- To compare the sensitivity of BWD and LAL tests in detecting endotoxin-related toxicity in DTaP vaccines.
- To investigate potential interference with standard safety assays in certain vaccine batches.
Main Methods:
- Mouse body weight decreasing (BWD) toxicity test.
- Limulus amaebocyte lysate (LAL) assay.
- Lipopolysaccharide (LPS) spiking experiments to assess assay interference.
- Pyrogenicity and prostaglandin E(2) induction assays.
Main Results:
- Three of four imported DTaP vaccine batches exhibited significant BWD toxicity.
- LAL test results showed no marked difference between imported and Japanese DTaP vaccines despite BWD toxicity.
- One imported DTaP batch demonstrated strong interference with LAL activity, pyrogenicity, and prostaglandin E(2) induction.
Conclusions:
- The BWD toxicity test is a sensitive method for detecting endotoxin-related toxicity in DTaP vaccines.
- The LAL test may not be sufficient for assessing the safety of DTaP vaccines with interfering substances.
- In vivo testing may be necessary for ensuring the safety of DTaP vaccines that interfere with in vitro assays.
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