Toward a new vaccine for pertussis

Abstract

To overcome the limitations of the current pertussis vaccines, those of limited duration of action and failure to induce direct killing of Bordetella pertussis , a synthetic scheme was devised for preparing a conjugate vaccine composed of the Bordetella bronchiseptica core oligosaccharide with one terminal trisaccharide to aminooxylated BSA via their terminal ketodeoxyoctanate residues. Conjugate-induced antibodies, by a fraction of an estimated human dose injected into young outbred mice as a saline solution, were bactericidal against B. pertussis , and their titers correlated with their ELISA values. The carrier protein is planned to be genetically altered pertussis toxoid. Such conjugates are easy to prepare, stable, and should add both to the level and duration of immunity induced by current vaccine-induced pertussis antibodies and reduce the circulation of B. pertussis .

Pertussis: Microbiology, Disease, Treatment, and Prevention

“…Since then, the reported number of pertussis cases in Japan has been low (494)(495)(496). These results from Japan encouraged other developed countries to evaluate Japanese DTaP vaccines and to develop DTaP vaccines with additional antigens.…”

“…Some vaccine experts believe that the relatively short duration of immunity offered by acellular pertussis vaccines is the most important factor that explains the trends of outbreaks, particularly among children 7 to 10 years old (193,496). For example, during the California outbreak, children primed with DTP vaccines had longer-lasting immunity than those primed with DTaP (502).…”

Investigating Pertussis Toxin and its Impact on Vaccination

“…It has been proposed that the efficacy of the monocomponent PTX vaccine, when given at high dosage, is similar to that of the multicomponents aPV and that therefore PTX is both an essential and sufficient antigen in aPV. In order to improve PTX-based aPV, a genetically detoxified PTX protein (9K/129G) has recently been used as a carrier for lipooligosaccharide (LOS) from B. pertussis to induce both anti-PTX and bactericidal anti-LOS antibodies [26]. However, the protective efficacy in mouse potency assays or in clinical studies has not been documented yet.…”

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

“…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. Improvements/additions to current aP vaccines could include changing to genetically detoxified PT and inclusion of additional virulence factors such as adenylate cyclase toxin and lipooligosaccharide conjugates to broaden the immune response [27,28]. New vaccine adjuvants have been developed, but underlying concerns about safety will make their introduction into thirdgeneration pertussis vaccines destined for use in infants challenging.…”