In vitro alternative for reactogenicity assessment of outer membrane vesicle based vaccines

Area of Science:

• Vaccinology
• Immunology
• Toxicology

Background:

• Immune activating molecules in vaccines enhance efficacy but can increase reactogenicity.
• Regulatory agencies mandate rabbit pyrogen testing (RPT) to assess vaccine reactogenicity.
• The monocyte activation test (MAT) is an emerging in vitro alternative, but requires adaptation for pyrogen-containing vaccines.

Purpose of the Study:

• To adapt the MAT for testing pyrogen-containing vaccines in early development.
• To compare MAT and RPT for assessing the safety of pertussis outer membrane vesicle (OMV) vaccine candidates.
• To evaluate the MAT's utility in vaccine development and its potential to replace RPT.

Main Methods:

• Comparison of MAT and RPT using pertussis OMV vaccine candidates and Bexsero as a reference.
• Assessment of reactogenicity profiles, including TLR2 and TLR4 activation by pertussis OMVs.
• Evaluation of modifications such as dose adjustment, LPS alteration, and intranasal administration.

Main Results:

• Pertussis OMVs with wild-type LPS showed higher reactogenicity than Bexsero, activating TLR2 and TLR4.
• Reactogenicity of pertussis OMVs was modulated by dose, LPS modification, and administration route.
• MAT and RPT yielded comparable reactogenicity profiles, except for LPS-modified products.

Conclusions:

• The adapted MAT is applicable for assessing reactogenicity of pyrogen-containing vaccines during development.
• Pertussis OMV vaccine candidates demonstrated an acceptable safety profile.
• The MAT shows potential to replace traditional rabbit pyrogen testing (RPT).