A Pertussis Outer Membrane Vesicle-Based Vaccine Induces Lung-Resident Memory CD4 T Cells and Protection Against Bordetella pertussis, Including Pertactin Deficient Strains

ZURITA, MARÍA EUGENIA; WILK, MIESZKO M.; CARRIQUIRIBORDE, FRANCISCO; BARTEL, ERIKA; MORENO, GRISELDA; MISIAK, ALICJA; MILLS, KINGSTON H. G.; HOZBOR, DANIELA

Frontiers in Cellular and Infection Microbiology

Frontiers Media SA

Año: 2019 vol. 9

Pertussis is a respiratory infectious disease that has been resurged during the lastdecades. The change from the traditional multi-antigen whole-cell pertussis (wP)vaccines to acellular pertussis (aP) vaccines that consist of a few antigens formulated withalum, appears to be a key factor in the resurgence of pertussis inmany countries. Thoughcurrent aP vaccines have helped to reduce the morbidity and mortality associatedwith pertussis, they do not provide durable immunity or adequate protection againstthe disease caused by the current circulating strains of Bordetella pertussis, whichhave evolved in the face of the selection pressure induced by the vaccines. Basedon the hypothesis that a new vaccine containing multiple antigens could overcomedeficiencies in the current aP vaccines, we have designed and characterized a vaccinecandidate based on outer membrane vesicle (OMVs). Here we show that the OMVsvaccine, but not an aP vaccine, protected mice against lung infection with a circulatingpertactin (PRN)-deficient isolate. Using isogenic bacteria that in principle only differ inPRN expression, we found that deficiency in PRN appears to be largely responsible forthe failure of the aP vaccine to protect against this circulating clinical isolates. Regardingthe durability of induced immunity, we have already reported that the OMV vaccine isable to induce long-lasting immune responses that effectively prevent infection with B.pertussis. Consistent with this, here we found that CD4 T cells with a tissue-residentmemory (TRM) cell phenotype (CD44+CD62LlowCD69+ and/or CD103+) accumulatedin the lungs of mice 14 days after immunization with 2 doses of the OMVs vaccine.CD4 TRM cells, which have previously been shown to play a critical role sustainedprotective immunity against B. pertussis, were also detected in mice immunizedwith wP vaccine, but not in the animals immunized with a commercial aP vaccine.Zurita et al. Pertussis OMVs Vaccine Induces TRM-CellsThe CD4 TRM cells secreted IFN-g and IL-17 and were significantly expanded throughlocal proliferation following respiratory challenge of mice with B. pertussis. Our findingsthat the OMVs vaccine induce respiratory CD4 TRM cells may explain the ability of thisvaccine to induce long-term protection and is therefore an ideal candidate for a thirdgeneration vaccine against B. pertussis.