B. pertussis causes a severe respiratory disease (whooping cough) in young infants associated with high mortality rates. The acellular pertussis vaccine has been part of the routine pediatric immunization schedule as a component of the Diphtheria-Tetanus vaccine (DTaP) for over two decades. Despite extensive vaccination, pertussis cases continue to emerge, the majority in infants <3 months of age who have not completed the primary vaccination series. One of the proposed reasons for this increased incidence has been the failure of the acellular pertussis vaccine to provide robust long-lasting protective immunity. On the basis of raising antibody levels in the population, immunization of mothers and other household members has been recommended to reduce exposure to young infants. The immune responses to the acellular pertussis vaccine elicited in infants and during pregnancy are not thoroughly known and firm correlates of protection remain to be established. A better understanding of protective immunity necessary to prevent B. pertussis infection is required to seek out more effective vaccines. IgA is commonly viewed as essential for protection against mucosal pathogens, but strong systemic IgG responses are generated following parenteral vaccination with DTaP in children and Tdap in adults; the same trend is seen in animal models. In this application we propose to study the role of vaccine-induced IgG in protection against B. pertussis in the context of both maternal and infant immunization and the mechanisms involved, specifically the antimicrobial capacity of anti-B. pertussis IgG and the processes involved in translocation through the mucosa and into the airways. We will test the hypothesis that maternal and infant vaccine-induced IgG actively transported through the respiratory mucosa via the neonatal Fc receptor (FcRn) deploys functional antimicrobial properties and mediates protection against B. pertussis infection.
In Specific Aim 1, we will examine the contribution of pertussis-specific IgG induced through maternal vaccination and transferred to offspring via placenta and/or milk in protection against pertussis infection and examine the involvement of the FcRn in the transport of milk IgG from the intestinal lumen into circulation and of circulating IgG across epithelium in the respiratory tract and into the airways for protection against infection.
In Specific Aim 2, we will examine the contribution of IgG produced in infants immunized with DTaP in protection against pertussis, their functional capacity and FcRn-mediated translocation to the respiratory airways. This work has the potential to identify a mechanism that can explain how IgG protects against B. pertussis infection.
Pertussis (whooping cough) is a highly contagious respiratory infection that predominantly affects infants too young to have completed the primary vaccination series. Despite high vaccination rates, a dramatic resurgence of pertussis has been seen in recent years. To provide a rational basis for improving current immunization strategies, we propose to examine the role of vaccine-induced IgG in protection against B. pertussis in the context of maternal and infant immunization and the mechanisms involved, specifically, the functional antimicrobial capacity and processes that allow IgG translocation through the mucosal epithelium into the respiratory airways.
