PRIME-BOOST STRATEGY AGAINST PERTUSSIS IN MICE: BENEFITS AND MECHANISMS

GAILLARD, MARÍA EMILIA; ZURITA E; HOZBOR D; BOTTERO D

Bruselas

Simposio; 12 th Bordetella Symposium; 2019

Differences between current pertussis vaccines could explain, at least in part, the worrying pertussisepidemiological situa;on described in countries that only use acellular vaccine (aP) in their calendar.While classical whole cell vaccine (wP) induces rela;ve long-term protec;on and promotes Th1/Th17responses; acellular vaccine induces Th2 profile and their induced immunity wanes faster than wP. Wehave already iden;fied and characterized a vaccine candidate based on outer membrane vesicles (OMVs)that has been shown to be safe and able to induce protec;on in mice, with a mixed Th1/Th17/Th2 profileand a robust an;body response. Since prime-boost vaccine strategies could enhance cellular and humoralimmunity, we evaluated the performance of heterologous prime-boost strategies, using the OMVs basedvaccine to prime mice and commercial aP vaccine as booster. One month aher the last immuniza;on, weevaluated the humoral and cell-mediated immune responses induced. For compara;ve purpose, aschedule consis;ng in two doses, one with aP and the second with OMVs (aP-OMVs) was also analyzed.Treatments with two doses of aP or non-vaccinated were used as controls. We detected significantlyhigher levels of Total IgG against B. pertussis in sera of mice primed with OMVs based vaccine (294.3±37.1)in comparison with other treatments (p0.05). Of interest was that the OMVs-aP-generated sera hadbactericidal capabili;es that were not detected with any other induced sera, sugges;ng that this ac;vitywas involved in the clearance of B. pertussis detected using the intranasal challenge mouse model.Regarding IgG2a/IgG1, high ra;o was observed for OMVs-aP treatment, sugges;ng that OMVs skewed theimmune response to a Th1 profile. S;mula;on of cultured spleen cells from immunized mice with OMVsaPschedule resulted in high levels of IFN-γ and interleukin-17 produc;on. These results support theheterologous prime-boost strategy as an alterna;ve to be considered to improve pertussis control.