Pertussis: acellular, whole-cell, new vaccines, what to choose?

Pertussis or whooping cough, caused by Bordetella pertussis, is a severe respiratory disease that can be fatal in young infants. Two types of vaccines are available and widely used, firstgeneration whole-cell vaccines (wPV) and more recent acellular vaccines (aPV). Nevertheless, pertussis is still not under control, and its incidence is rising in several countries that have switched from wPV to aPV. Both protect against disease, but none of them prevents infection, as shown in a recently developed baboon model. Yet, asymptomatic B. pertussis transmission may be the single most important cause for the resurgence of pertussis. Vaccines that prevent infection in addition to disease are needed to ultimately control whooping cough. Although one such vaccine is in clinical development, it will still take years before it can be used. Meanwhile, recent evidence shows that aPV is effective for vaccination during pregnancy to protect the newborns against severe and deadly pertussis. Pertussis or whooping cough, caused by Bordetella pertussis, is a severe respiratory childhood disease that can be fatal, especially in very young infants. However, it also represents a significant disease burden in older children, adolescents, and adults [1]. Efficacious vaccines against pertussis are available since the middle of the last century, and global vaccination coverage for the three primary vaccine doses has now reached >85% [2]. Nevertheless, the disease is still not under control and is today the most prevalent vaccine-preventable childhood disease. The World Health Organization (WHO) records close to 200,000 pertussis-related deaths and more than 16 million yearly pertussis cases globally [3]. However, before the implementation of mass vaccination the reported incidence of the disease in countries like the U.S. was as high as 150 cases per 100,000 population, which was likely a vast underestimation [4]. Since the 1950s, the incidence and the numbers of pertussis-linked deaths have declined dramatically to reach a nadir in the late 1970s in several countries, illustrating the effectiveness of mass vaccination against pertussis. However, more recently, the numbers of cases and associated deaths have again increased in several industrialized countries, illustrating, in turn, the shortcomings of current vaccination strategies. Two types of pertussis vaccines are currently available, the first-generation whole-cell vaccines (wPV) and the more recent acellular vaccines (aPV), composed of one to five purified antigens. All available pertussis vaccines are combined with tetanus and diphtheria toxoids and many also with hepatitis B, inactivated polio, and Haemophilus influenza B polysaccharide [5]. The efficacy of wPV has been demonstrated to be >90% after three administrations, although the efficacy of some wPV was as low as 30–50% [6]. The more defined aPV have been developed in the 1980, subsequent to local and systemic adverse events that have been associated with wPV, but also because of the difficulties in lot consistency. All contain inactivated pertussis toxin, most of them contain also filamentous haemagglutinin, many contain pertactin in addition and some contain also fimbriae. They have a clearly improved safety profile over wPV [5], and their short-term efficacy after three administrations was estimated to be 67–70% and even 84% for vaccines containing three or five B. pertussis components. However, when compared in these short-term studies to well-performing wPV, the efficacy of aPV was slightly lower. Because of their improved safety profile and similar efficacy, most industrialized countries have replaced wPV with aPV. Nevertheless, wPV are still the most used vaccine globally, mostly because of the high cost of aPV, difficult to afford in resource-poor countries. In recent years, it has become apparent that immunity induced by aPV wanes substantially faster than that induced by wPV [7], which led the Strategic Advisory Group of Experts on Immunization at the WHO (WHO/SAGE) to recommend that countries considering a switch from wPV to aPV should await further guidance [8]. However, increases in pertussis incidence have also been observed in countries in which wPV continue to be used. Thus waning immunity induced by aPV is not the only reason for the resurgence of pertussis. A study based on mathematical modeling concluded that asymptomatic transmission is the most parsimonious explanation of the current resurgence of B. pertussis [9]. Results coming from a recently developed baboon model suggest that aPV does not prevent transmission of B. pertussis, even though it protects against disease, and that neither aPV, nor wPV prevents infection by virulent B. pertussis, although, wPV-vaccinated animals appeared to clear the infection faster than aPV-vaccinated baboons [10]. Nevertheless, the total bacterial burden was lower in the vaccinated compared to the naïve animals,