Antibody Mediated Protection in Whooping Cough Infection Due to Bordetella Pertussis

Incidence rates of whooping cough, a highly infectious disease caused primarily in humans by the bacteria, Bordetella pertussis (B. pertussis), decreased dramatically as result of whole cell pertussis (wP) immunizations. Concerns about the safety of the wP vaccines resulted in the development of new vaccines using acellular components of B. pertussis. In spite of widespread vaccine availability, whooping cough continues to affect infants and young children, often with serious consequences. Disease rates in developing countries have risen steadily over the last few decades to 42,000 cases in 2012.  The safer acellular pertussis (aP) vaccines prevent the severe manifestations of the disease but are unable to completely eliminate subclinical infection. 

 In order to design improved vaccines, it is important to understand the mechanisms which induce protective immunity to the pertussis bacteria. My research work aims to better understand the biochemical attributes of antibodies produced after humans receive an aP vaccination. Of the numerous B. pertussis antigens, the pertussis toxin (PTx) and filamentous hemagglutinin (FHA) have been identified as major factors which elicit a humoral response sufficient for protection. After booster immunization with an aP vaccine, representatives of monoclonal antibodies responding to PTx or FHA were expressed and purified. The affinity and neutralizing ability to the antigens were also measured and the epitopes recognized are currently being classified. The results of this study are expected to expand the present knowledge of the molecular mechanisms of antibody mediated protection after aP vaccination and improve the design of the vaccines. The study also identifies antibody candidates which neutralize PTx or FHA and maybe useful for passive immunotherapy of whooping cough.