Abstract
The pertussis vaccination is highly recommended for infants, children, and pregnant women. Despite a high coverage of vaccination, pertussis continues to be of public health concern as a re-emerging infectious disease. The mechanism by which vaccine-elicited anti-pertussis antibodies mediate direct bactericidal effects is poorly understood. In this study, we showed that the interaction of B. pertussis with A549 epithelial cells induce release of biological factors which enhance bacteria growth. Complement-depleted antisera from vaccine-immunized guinea pigs or monoclonal antibodies targeting FHA and FIM mediate bacteria aggregation and elicit bactericidal effects. Our in vitro results indicated that aggregation of bacteria through anti-FIM and anti-FHA specific antibodies is one of the major biological mechanisms to clear bacterial infections and restore epithelial cell survival in vitro. Our data also indicates that the anti-pertussis antibodies reduce secretion of proinflammatory chemokines and cytokines by preventing interaction of B. pertussis with host cells. The results of this study not only demonstrate mechanism of action of anti-FIM and anti-FHA antibodies, but also opens translational applications for potential therapeutic approaches or development of analytical assays such as in vitro potency assays.
Highlights
Pertussis, known as whooping cough, is a re-emerging infectious disease in many countries despite high coverage of vaccines [1, 2]
We showed that both anti-fimbriae and 3 (FIM) and antiFHA sera and monoclonal antibodies (mAbs) induce B. pertussis aggregation and bacterial cell death, reducing bacterial growth
In a co-culture system, we observed that bacterial growth was increased in the presence of A549 epithelial cells in a dose-dependent manner, compared to B. pertussis cultured alone in complete Dulbecco’s Modified Eagle Medium (DMEM) media (Figure 1A)
Summary
Known as whooping cough, is a re-emerging infectious disease in many countries despite high coverage of vaccines [1, 2]. This life-threatening contagious disease is caused by the Gram-negative bacterium, Bordetella pertussis. For an effective control of pertussis, it is recommended to strengthen vaccination coverage among the whole population by providing primary vaccination to newborns, and boosting infants and adults every 10 years [6]. Studies have shown strong humoral protection in infants; the mechanism by which antibodies control B. pertussis infection has not been well understood [9, 11, 12]
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