T- and B-Cell-Mediated Protection Induced by Novel, Live Attenuated Pertussis Vaccine in Mice. Cross Protection against Parapertussis

Abstract

BackgroundDespite the extensive use of efficacious vaccines, pertussis still ranks among the major causes of childhood mortality worldwide. Two types of pertussis vaccines are currently available, whole-cell, and the more recent acellular vaccines. Because of reduced reactogenicity and comparable efficacy acellular vaccines progressively replace whole-cell vaccines. However, both types require repeated administrations for optimal efficacy. We have recently developed a live attenuated vaccine candidate, named BPZE1, able to protect infant mice after a single nasal administration.Methodology/Principal FindingsWe determined the protective mechanism of BPZE1-mediated immunity by using passive transfer of T cells and antibodies from BPZE1-immunized mice to SCID mice. Clearance of Bordetella pertussis from the lungs was mediated by both BPZE1-induced antibodies and CD4+, but not by CD8+ T cells. The protective CD4+ T cells comprised IFN-γ-producing and IL-17-producing subsets, indicating that BPZE1 induces both Th1 and Th17 CD4+ T cells. In addition, and in contrast to acellular pertussis vaccines, BPZE1 also cross-protected against Bordetella parapertussis infection, but in this case only the transfer of CD4+ T cells conferred protection. Serum from BPZE1-immunized mice was not able to kill B. parapertussis and did not protect SCID mice against B. parapertussis infection.Conclusions/SignificanceThe novel live attenuated pertussis vaccine BPZE1 protects in a pre-clinical mouse model against B. pertussis challenge by both BPZE1-induced antibodies and CD4+ T cell responses. It also protects against B. parapertussis infection. However, in this case protection is only T cell mediated.

Live attenuated pertussis vaccine BPZE1 induces a broad antibody response in humans

“…Although early studies indicated that CD8 + T cells are not necessary for protection against pertussis (39,40), recent data IgA memory B cells may be a consequence of the slow onset of PT expression during the colonization process in the nasal cavity, unlike FHA, PRN, and FIM, which are fully expressed during initial stages of colonization (43). In any event, these data suggest that B. pertussis antigens other than PT in BPZE1 do elicit an IgA response.…”

Non-specific Effects of Live Attenuated Pertussis Vaccine Against Heterologous Infectious and Inflammatory Diseases

“…A single nasal BPZE1 vaccination led to strong protection against colonization by B. parapertussis (9) and protection could be transferred by splenocytes but not by serum of BPZE1-vaccinated mice, whereas serum from convalescent mice was able to protect against re-challenge with B. parapertussis . These observations indicate that BPZE1-mediated cross-protection was cell-mediated (12). Bordetella bronchiseptica can infect a large variety of mammalian species, including humans, and can cause mild to severe cough.…”

“…In addition to B. pertussis , BPZE1 protects mice also against lung infection by other Bordetella species, although this was not observed after vaccination with aPV (9, 12, 19). Bordetella parapertussis is a respiratory pathogen that causes chronic pneumonia in sheep or pertussis-like disease in humans, albeit usually less serious than pertussis caused by B. pertussis .…”

Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity

“…More recently, the ability of B. pertussis to skew the host immune response towards the expansion of Th17 cells was observed. In mice, pertussis infection or immunization with the whole cell vaccine induce a Th17 response and the generation of antigen-specific Th17 cells correlates with protection [ 32 , 33 , 34 , 35 ]. In agreement with these results, it has been shown that human monocyte-derived DC infected ex vivo with B. pertussis induce a mixed Th1/Th17 polarization of CD4 + T cells [ 36 , 37 ].…”