Development of Affordable Effective Vaccines against Whooping Cough for the Developing World

Abstract

The rate of mortality in children associated with serious infectious diseases is significantly higher in the developing world and in socioeconomically disadvantaged populations in developed industrialized countries. The reasons underpinning the higher incidence of whooping cough (pertussis) in these populations include overcrowding and poor hygiene, poor coverage with available pertussis containing vaccines and waning immunity following immunisation and infection. Two types of vaccines are currently used for vaccinating infants and children. The whole cell pertussis vaccine, the most used vaccine worldwide, consisting of a killed B pertussis strain, origin of which may differ in different countries, is generally given in combination with chemically or genetically inactivated diphtheria and tetanus toxoids [DTwP or DTPw], with or without combination with Haemophilus influenzae type b [Hib], hepatitis B or inactivated polio virus vaccine [IPV], depending upon the vaccine manufacturer. This vaccine played a pivotal role in reducing the whooping cough morbidities and mortalities in the 1940’s [1]. Because of the perceived seriousness of the side reactions particularly febrile prolonged convulsions or encephalopathy, albeit in insignificant number of vaccinees, has been reported in temporal association with DTwP vaccination [2], the whole cell vaccine was replaced by acellular pertussis vaccine formulations [DTaP] due to better reactogenicity profiles [3]. The aP component in the DTaP formulations consist of chemically or genetically inactivated/detoxified pertussis toxin [dPT], filamentous haemagglutinin [FHA] and pertactin [PRN] with or without fimbrial antigens [FIM]. Other components in the DTaP vaccine formulation are the same as mentioned above for the DTwP vaccine with or without combination with Hib, hepatitis B or inactivated poliovirus vaccine [IPV], depending upon the vaccine manufacturer. The resurgence of pertussis epidemics worldwide and increased proportions of cases in older children and adults, led to the