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. To improve the disease control, a new generation of vaccines capable to overcome those weaknesses associated to the current vaccines need to be developed. Previously we have demonstrated that the outer membrane vesicles obtained from the recombinant Bordetella pertussis strain expressing PagL enzyme (OMVsBpPagL) are good vaccine candidates to protect against pertussis. 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 BALB/c mice were immunized with TdapOMVsBpPagL and challenged with sublethal doses of the clinical isolate Bp106 selected as a representative circulating isolate. Comparisons with a current commercial Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of TdapOMVsBpPagL were performed. With the normalized doses of both vaccines we observed that TdapOMVsBpPagL protected against the clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. Regarding long-term immunity we observed that the TdapOMVsBpPagL protective capacity against the recommended WHO reference strain persisted at least 9 months. In agreement with these results TdapOMVsBpPagL induced Th1 and Th2 immune response. In contrast, commercial Tdap 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.