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.

Development of improved pertussis vaccine

“…Several pathways deserve to be explored even without there being a universal solution, since each country has a different situation depending on the history of vaccination policy developed in the last decades. One possibility is to promote the use of wP vaccines but with new less reactogenic 34 and improved 35 formulations. However, the return to wP vaccine use would be difficult for the public to accept in countries that switched to aP vaccines due to adverse reactions from wP vaccines.…”

Immunization against Pertussis: An Almost Solved Problem or a Headache in Public Health

“…The introduction of procedures that increase the safety of wP vaccines maintaining its efectiveness remains a very important aspect, especially for developing countries that do not have access to currently available aP vaccines. In this sense, a whole cell pertussis vaccine was developed with low endotoxicity (Plow) obtained by chemical extraction of the LOS fraction from the outer membrane of the bacterial cell [105]. This vaccine was evaluated as DTwP vaccine, combined with tetanus and diphtheria toxoids in a Phase I ield trial in infants, showing to be less reactogenic and equally immunogenic and protective as the traditional DTP vaccine [106].…”

Shortcomings of pertussis vaccines: why we need a third generation vaccine

“…A novel live-attenuated B. pertussis strain known as BPZE1 is being investigated for intranasal administration at birth [25]. wP with chemically extracted lipopolysaccharide has been explored in mice with early evidence of improved tolerability [26]. Third-generation pertussis vaccines that contain a large number of purified components might show more diverse protection and improved resistance to genetic mutations with acceptable reactogenicity.…”