An improved whole cell pertussis vaccine with reduced content of endotoxin

An improved whole cell pertussis vaccine with reduced content of endotoxin

An improved whole cell pertussis vaccine, designated as Plow, which is low in endotoxicity due to a chemical extraction of lipo-oligosaccharide (LOS) from the outer membrane, was evaluated for safety, immunogenicity and potency, comparatively to a traditional whole cell pertussis vaccine. Current wh...

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Bibliographic Details
Published in:Human vaccines & immunotherapeutics Vol. 9; no. 2; pp. 339 - 348
Main Authors: Dias, Waldely, van der Ark, Arno A.J., Sakauchi, Maria Aparecida, Kubrusly, Flávia Saldanha, Prestes, Ana Fabíola R.O., Borges, Monamaris Marques, Furuyama, Noemi, Horton, Denise S.P.Q., Quintilio, Wagner, Antoniazi, Marta, Kuipers, Betsy, van der Zeijst, Bernard A.M., Raw, Isaias
Format: Journal Article
Language:English
Published: United States Taylor & Francis 01-02-2013
Landes Bioscience
Subjects:
Animals
Bordetella pertussis
Drug Stability
endotoxicity
Endotoxins - analysis
Endotoxins - isolation & purification
Female
immunogenicity
lypo-oligosaccharide
Mice
Pertussis Vaccine - administration & dosage
Pertussis Vaccine - adverse effects
Pertussis Vaccine - chemistry
Pertussis Vaccine - immunology
pertussis vaccines
Rabbits
reactogenicity
Research Paper
safety
Vaccine Potency
endotoxicity
pertussis vaccines
safety
reactogenicity
Bordetella pertussis
lypo-oligosaccharide
immunogenicity
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Summary:An improved whole cell pertussis vaccine, designated as Plow, which is low in endotoxicity due to a chemical extraction of lipo-oligosaccharide (LOS) from the outer membrane, was evaluated for safety, immunogenicity and potency, comparatively to a traditional whole cell pertussis vaccine. Current whole cell pertussis vaccines are effective but contain large quantities of endotoxin and consequently display local and systemic adverse reactions after administration. Endotoxin is highly inflammatory and contributes considerably to the reactogenicity as well as the potency of these vaccines. In contrast, acellular pertussis vaccines hardly contain endotoxin and are significantly less reactogenic, but their elevated costs limit their global use, especially in developing countries. In this paper, bulk products of Plow and a traditional whole cell vaccine, formulated as plain monocomponents or combined with diphtheria and tetanus toxoids (DTPlow or DTP, respectively) were compared by in vitro and in vivo assays. Chemical extraction of LOS resulted in a significant decrease in endotoxin content (20%) and a striking decline in endotoxin related toxicity (up to 97%), depending on the used in vitro or in vivo test. The LOS extraction did not affect the integrity of the product and, more importantly, did not affect the potency and/or stability of DTPlow. Moreover, hardly any differences in antibody and T-cell responses were observed. The development of Plow is a significant improvement regarding the endotoxicity of whole cell pertussis vaccines and therefore a promising and affordable alternative to currently available whole cell or acellular pertussis vaccines for developing countries.
ISSN:2164-5515
2164-554X
DOI:10.4161/hv.22847