title: An improved whole cell pertussis vaccine with reduced content of endotoxin.
abstract: 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.
authors.affiliation: Center of Biotechnology; Instituto Butantan; São Paulo, Brazil.
authors.forename: Waldely Oliveira
authors.initials: WO
authors.lastname: Dias
authors.forename: Arno A J
authors.initials: AA
authors.lastname: van der Ark
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Sakauchi
authors.forename: Flávia Saldanha
authors.initials: FS
authors.lastname: Kubrusly
authors.forename: Ana Fabíola R O
authors.initials: AF
authors.lastname: Prestes
authors.forename: Monamaris Marques
authors.initials: MM
authors.lastname: Borges
authors.forename: Noemi
authors.initials: N
authors.lastname: Furuyama
authors.forename: Denise S P Q
authors.initials: DS
authors.lastname: Horton
authors.forename: Wagner
authors.initials: W
authors.lastname: Quintilio
authors.forename: Marta
authors.initials: M
authors.lastname: Antoniazi
authors.forename: Betsy
authors.initials: B
authors.lastname: Kuipers
authors.forename: Bernard A M
authors.initials: BA
authors.lastname: van der Zeijst
authors.forename: Isaias
authors.initials: I
authors.lastname: Raw
mesh_terms: D000818:Animals; D004355:Drug Stability; D004731:Endotoxins / Q000032:analysis / Q000302:isolation & purification*; D005260:Female; D051379:Mice; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D064166:Vaccine Potency
chemical_list: D004731:Endotoxins; D010567:Pertussis Vaccine
keywords: Bordetella pertussis; endotoxicity; immunogenicity; lypo-oligosaccharide; pertussis vaccines; reactogenicity; safety