Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes

MARIA EMILA GAILLARD; DANIELA BOTTERO; AGUSTINA ERREA; MAXIMILIANO ORMAZABAL; EUGENIA ZURITA; GRISELDA MORENO; MARTIN RUMBO; DANIELA HOZBOR

VACCINE

ELSEVIER SCI LTD

Lugar: Amsterdam; Año: 2014 p. 931 - 937

0264-410X

Despite high vaccination coverage rates, pertussis continues to be a global concern, with increased incidence widely noted. The current pertussis epidemiologic situation has been mainly attributed to waning immunity and pathogen adaptation. These two factors are recently proposed as two sides of the same coin: pathogen adaptations have decreased the period in which pertussis vaccines are effective and thus enhanced the waning of immunity. To improve the disease control, it seems to be necessary a new generation of vaccines capable to overcome those weaknesses associated to the current pertussis vaccines. Previously we have demonstrated that the outer membrane vesicles (OMVs) obtained from B. pertussis are good vaccine candidates to protect against pertussis. Moreover, OMVs obtained from recombinant B. pertussis strain expressing PagL enzyme constitute a safer formulation (OMVsBpPagL), without altering protective immunity. In this work the OMVsBpPagL formulated with diphtheria and tetanus toxoids (TdapOMVsBpPagL) was used to evaluate its capacity to offer protection against Argentinean clinical isolates and to induce long-term immunity. To these aims we immunized BALB/c mice with TdapOMVsBpPagL and challenged with sublethal doses of the clinical isolate Bp106 selected as a representative circulating isolate. Comparisons with a current commercially acellular combined pertussis vaccine (commercial Tdap vaccine) were performed. For these comparisons, commercial Tdap vaccine was used at a dose in which pertussis toxin (PTx) level was equivalent to that of TdapOMVsBpPagL. We selected PTx antigen to normalize the dose of vaccines used since we observed that the protective capacity of the OMVs significantly diminished when the OMVs were obtained from a B. pertussis mutant strain that does not expresses PTx. With the selected doses of both acellular vaccines, 3 μg of protein for TdapOMVsBpPagL and 1/200 of human dose for commercial Tdap, we observed that TdapOMVsBpPagL protected against the Argentinean clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. Commercial Tdap exhibited high protection level when it was used at a high dose (1/10 of the human dose). Regarding long-term immunity we observed that the TdapOMVsBpPagL protective capacity against the recommended WHO reference strain, Bp 18323, persisted at least 9 months. In agreement with these results TdapOMVsBpPagL induced Th1 and Th2 immune response. In contrast, a current licensed Tdap, administered with alum as the adjuvant, induced Th2 but weak Th1 responses. All results presented here showed that TdapOMVsBpPagL is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine.