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.

Whooping cough or pertussis is a serious infectious disease of the human respiratory tract, caused by Gram-negative bacteria Bordetella pertussis and Bordetella parapertussis HU . The current pertussis vaccines may consist of dead cells of B. pertussis (whole cell pertussis vaccines-wPs) or purified antigens from the bacterium (acellular pertussis vaccines-aPs). The aPs are less reactogenic and have been widely used in developed countries for more than two decades, but their high cost of production makes them prohibitive for developing countries, and the accelerated rate of epidemic outbreaks has led to the hypothesis that aPs are less effective than the wP ones. Considering cost-effectiveness, some authors have pointed out questions about the possibility of reintroduction of wP vaccines into the primary doses of pertussis vaccination. The Butantan Institute in São Paulo, Brazil, developed a wP vaccine with low endotoxicity (Plow) obtained by chemical extraction of the lipooligosaccharide (LOS) fraction from the outer membrane of the bacterial cell, showing to be less reactogenic and equally immunogenic and protective as the traditional wP vaccine. The Plow may possibly be introduced into the vaccination schedule for immunization of adolescents and young adults in Brazil, an important epidemiological contribution to reducing the circulation of B. pertussis.