Related Experiment Video
Updated: Jan 19, 2026
Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Comparative transcriptomics between species attributes reactogenicity pathways induced by the capsular group B
Dylan Sheerin1, Daniel O'Connor2, Christina Dold2
1Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK. dylan.sheerin@paediatrics.ox.ac.uk.
Abstract:
The capsular group B meningococcal (MenB) four component vaccine (4CMenB) has been licensed for the prevention of invasive disease caused by MenB. The vaccine causes fever in infants, particularly when given in combination (concomitant) with other routinely-administered vaccines (routine), such as the standard diphtheria, tetanus, pertussis (DTP)-containing vaccine. To assess the suitability of a mouse immunisation model to study this phenomenon, we monitored temperature in mice after a second dose of routine vaccines, with or without 4CMenB, and compared the results with those in humans. Using this mouse model, we explored the reactogenicity of 4CMenB components by measuring changes in temperature, cytokines, and gene expression induced by 4CMenB, one of its components, wild-type or attenuated endotoxin outer membrane vesicles (OMVs), or lipopolysaccharide (LPS). A significant rise (p < 0.01) in temperature was observed in mice immunised with 4CMenB, wild-type OMVs, and LPS. RNA-sequencing of mouse whole blood revealed a gene signature shared by the 4CMenB, OMV, and LPS groups consisting of bacterial pattern recognition receptors and neutrophil activation marker genes. Sequencing of neutrophils isolated after concomitant 4CMenB identified cells expressing the OMV-associated genes Plek and Lcp1. Immunisation with 4CMenB or OMVs led to increased IL-6 in serum and significant upregulation (p < 0.0001) of prostaglandin-synthesising enzymes on brain tissue. These data demonstrate the suitability of a mouse model for assessing vaccine reactogenicity and strongly indicate that the fever following vaccination with 4CMenB in human infants is induced by endotoxin contained in the OMV component of the vaccine.
Insights
Fever after the four-component meningococcal B vaccine (4CMenB) in infants is caused by endotoxin in its outer membrane vesicle component. A mouse model confirmed this, showing similar temperature increases and gene expression patterns.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- The four-component meningococcal B vaccine (4CMenB) prevents invasive meningococcal disease.
- Fever is a common side effect in infants, especially when co-administered with routine vaccines like DTP.
- Understanding the mechanism of vaccine-induced fever is crucial for improving vaccine safety.
Purpose of the Study:
- To evaluate a mouse model for studying vaccine-induced fever.
- To investigate the reactogenicity of 4CMenB components.
- To identify the specific vaccine component responsible for fever.
Main Methods:
- Mice were immunized with routine vaccines, with or without 4CMenB, and body temperature was monitored.
- RNA-sequencing of whole blood and isolated neutrophils was performed to analyze gene expression.
- Cytokine levels (IL-6) and prostaglandin synthesis in brain tissue were measured.
Main Results:
- Mice immunized with 4CMenB, wild-type outer membrane vesicles (OMVs), or LPS showed significant temperature increases.
- A shared gene expression signature involving bacterial pattern recognition and neutrophil activation was observed.
- 4CMenB and OMV immunization led to increased IL-6 and upregulation of prostaglandin-synthesizing enzymes.
Conclusions:
- The mouse model is suitable for assessing vaccine reactogenicity.
- Fever following 4CMenB vaccination in humans is likely induced by the endotoxin within the OMV component.
- These findings provide insights into the mechanism of vaccine-induced fever.
