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

GAILLARD ME; BOTTERO DANIELA; ERREA AGUSTINA; ORMAZABAL MAXIMILIANO; ZURITA M. EUGENIA; MORENO GRISELDA; RUMBO MARTIN; PETER VAN DER LEY; ARNO VAN DER ARK; HOZBOR DANIELA

Simposio; 10th International Symposium on Bordetella; 2013

To improve the pertussis disease control it seems to be necessary a new generation of vaccines capable of conferring both long-lasting immunity and protection against different Bordetella genotypes. 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) were used to evaluate its capacity to offer protection against the clinical isolate Bp106, selected as representative of Argentinean circulating bacteria, and to induce long-term immunity. To these aims, BALB/c mice were immunized with TdapOMVsBpPagL and challenged with sublethal dose of B. pertussis. Significant differences between TdapOMVsBpPagL immunized animals and the negative control group were observed (p < 0.001). Comparisons with current commercial Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of TdapOMVsBpPagL were performed. TdapOMVsBpPagL protected against the Argentinean clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. The TdapOMVsBpPagL protective capacity persisted at least 9 months after immunization. The analysis of isotype distribution of the specific humoral response indicated that TdapOMVsBpPagL induced Th1 and Th2 responses. In contrast, the currently licensed Tdap, induced a Th2 but a weak Th1 response. All results presented here showed that TdapOMVsBpPagL is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine.