Alternative Safety Testing Strategies for Acellular Pertussis Vaccines

77 Infection by the Gram-negative bacterium Bordetella pertussis can lead to the development of pertussis, also known as whooping cough due to the characteristic sound infected infants make following a severe coughing fit. Infection by B. pertussis is fairly common, but it rarely causes serious complications in adults. However, the infection can be fatal in infants and young children if left untreated (CDC, 2011). Therefore, prevention of pertussis is a key health priority in most countries, and vaccination programs were initiated with the development of a killed whole-cell vaccine in the 1940’s. Although the whole-cell pertussis vaccine is effective, the incidence of mild adverse events (e.g., swelling and pain at the sight of injection, fever, drowsiness) and difficulties in the manufacture of a product with consistent quality, led to the development of less reactogenic acellular pertussis vaccines (Berbers et al., 2009). These vaccines contain purified components of the B. pertussis bacteria, which usually include bacterial hemagglutinin, pertactin, fimbriae 1 & 2, and inactivated pertussis toxin. Due to its biological activity, the pertussis toxin (Ptx) component of acellular pertussis vaccines must be inactivated prior to administration. This inactivation, or toxoiding, is most commonly done through the chemical modification of purified PTx to yield pertussis toxoid (PTd). To date, a number of chemical methods have been developed to inactivate Ptx, including the use of formaldehyde and/or glutaraldehyde, as well as hydrogen peroxide (Corbel and Xing, 2004). A genetically inactivated Ptx also has been developed (Peppoloni et al, 1995) but is not readily available. The chemical detoxification process for PTx must be carefully balanced between detoxification and maintenance of effective antigenic epitopes (Fig. 1). The chemical detoxification process modifies PTx to render its biochemical functions inacAlternative Safety Testing Strategies for Acellular Pertussis Vaccines