Evaluation of heterologous prime-boost immunization strategy against Bordetella pertussis using a novel outer membrane vesicle based vaccine and commercial acellular vaccine

ZURITA, MARIA EUGENIA; GAILLARD, M. EMILIA; MORENO, GRISELDA; SABATER, DAVID; RUMBO, MARTIN; HOZBOR, DANIELA

Mar del Plata

Congreso; SAIC . SAI . SAFE . 2016; 2016

Pertussis or whooping cough remains an important health problem in many countries even in those with high vaccination coverage. From 1950s-1990s this disease was controlled by use of whole cell pertussis (wP) vaccines. Later in 2000s these vaccines were replaced in most developed countries by acellular pertussis (aP) vaccines, made form purified components of Bordetella pertussis absorbed to alum. Unfortunately the new aP vaccines, although safer, are not as effective as the wP vaccine and this has been attributed to either 1) escape form protective immunity due to antigen variation in the bacterial antigens, 2) waning immunity following immunization with aP due to poor induction of immunological memory or 3) a failure of the aP vaccine to induced protective cellular immune responses. Under this context, we have developed a new vaccine candidate based on outer membrane vesicles (OMVs) derived from B. pertussis which is capable of inducing a more robust immune response than commercial aP vaccines with a Th2/Th1/Th17 cellular profile.Here we evaluated the immunogenicity of an heterologous prime-boost regimen using OMV-base and aP vaccines. For comparison purposes homologous vaccination regimens with OMV based vaccine and aP were also performed. For all tested cases, the induced humoral and cell-mediated immune responses were evaluated. A robust total IgG antibodies with a high IgG2a/IgG1 ratio were detected in sera of mice primed with OMV based vaccine, suggesting that OMVs skewed the immune response to a Th1 profile. Spleen cells from immunized mice were isolated and stimulated in vitro with B. pertussis antigens. Interestingly the obtained results showed that the priming with OMV vaccine induce a strong Th1/Th17 response with high values of INF-ϒ, which was maintained after aP boost. In contrast, IL-5 secretion was mainly produced by spleen cells from mice primed with aP, which results in a Th2 response. The immunological characterization in the murine model of these vaccination schedule led us to propose that OMVs are highly reliable primer candidates to be considered in future as an alternative strategy against pertussis.