Immunological Distinctions between Acellular and Whole-Cell Pertussis Immunizations of Baboons Persist for at Least One Year after Acellular Vaccine Boosting

While both whole-cell (wP) and acellular pertussis (aP) vaccines have been highly effective at reducing the global pertussis disease burden, there are concerns that compared to wP vaccination, the immune responses to aP vaccination may wane more rapidly. To gain insights into the vaccine elicited immune responses, pre-adult baboons were immunized with either aP or wP vaccines, boosted with an aP vaccine, and observed over a nearly two-year period. Priming with a wP vaccine elicited a more Th17-biased response than priming with aP, whereas priming with an aP vaccine led to a more Th2-biased response than priming with wP. These differences were maintained after aP vaccine boost immunizations. Compared to aP, animals primed with a wP vaccine exhibited greater numbers of pertussis specific memory B cells. While aP and wP vaccine priming initially elicited similar levels of anti-pertussis toxin antibody, titers declined more rapidly in aP vaccine primed animals leading to a 4-fold difference. Both wP and aP vaccine immunization could induce serum bactericidal activity (SBA); however, only one wP vaccine immunization was required to elicit SBA while multiple aP vaccine immunizations were required to elicit lower, less durable SBA titers. In conclusion, when compared to aP vaccine, priming with wP vaccine elicits distinct cellular and humoral immune responses that persist after aP vaccine boosting

Deciphering the domain specificity of C. difficile toxin neutralizing antibodies.

Clostridium difficile infection (CDI) is the principal cause of nosocomial diarrhea and pseudomembranous colitis associated with antibiotic therapy. The pathological effects of CDI are primarily attributed to toxins A (TcdA) and B (TcdB). Adequate toxin-specific antibody responses are associated with asymptomatic carriage, whereas insufficient humoral responses are associated with recurrent CDI. While the data supporting the importance of anti-toxin antibodies are substantial, clarity about the toxin domain specificity of these antibodies is more limited. To investigate this matter, combinations of human mAbs targeting multiple domains of TcdB were assessed using toxin neutralization assays. These data revealed that a combination of mAbs specific to all major toxin domains had improved neutralizing potency when compared to equivalent concentrations of a single mAb or a combination of mAbs against one or two domains. The function and toxin domain binding specificity of serum antibodies elicited by immunization of hamsters with a toxoid vaccine candidate was also assessed. Immunization with a toxoid vaccine candidate provoked toxin neutralizing antibodies specific to multiple domains of both TcdA and TcdB. When assessed in a toxin neutralization assay, polyclonal sera displayed greater activity against elevated concentrations of toxins than equivalent concentrations of individual mAbs. These data suggest a potential benefit of any antibody based therapeutic or prophylactic treatment that targets multiple toxin domains