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

GAILLARD M.E.; BOTTERO D.; AGUSTINA ERREA; ORMZABAL M.; ZURITA E; GRISELDA MORENO; MARTÍN RUMBO; D. HOZBOR

Dublin

Simposio; 10th International Symposium on Bordtella - Trinity Biomedical Sciences Institute (TBSI); 2013

To improve the pertussis disease control it seems to be necessary a new generation of vaccines capable of confering 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 candidate to protect against pertussis. Moreover, OMVs obtained from recombinant B. pertussis strain expressing PagL enzyme, a lipid A deacylase, constitute a safer formulation (OMVsBpPagL), without altering protective immunity. In this work the OMVsBpPagL formulated with diphtheria y tetanus toxoids (TdapOMVsBpPagL) was used to evaluate its capacity to offer protection against the clinical isolate Bp106 selected as representative of Argentinian circulating bacteria and to induce long-term immunity. To these aims we immunized BALB/c mice with TdapOMVsBpPagL and challenged with sublethal doses of  B. pertussis. Significant differences between TdapOMVsBpPagL immunized animals and the negative control group were observed (p < 0.001). Comparisons with currently commercially Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of TdapOMVsBpPagL were established. TdapOMVsBpPagL protected against Argentinean clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. The TdapOMVPagL induced long lasting humoral anti-OMV response and its proctective capacity persisted at least 9 months after immunization. The analysis of isotype distribution of the specific humoral response indicated that TdapOMVPagL induced Th1 and Th2 immune response. In contrast, a current licensed Tdap, , induced Th2 but weak Th1 responses. All results presented here showed that TdapOMVPagL is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine.