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

BACKGROUND: Despite 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 FINDINGS: We 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/SIGNIFICANCE: The 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.