title: A live, attenuated Bordetella pertussis vaccine provides long-term protection against virulent challenge in a murine model.
abstract: Despite successful mass vaccination programs, whooping cough remains a significant cause of neonatal mortality. Immunity induced by current vaccines wanes in adolescence, requiring additional immunizations to prevent resurgence. There is a need for a new generation of vaccines capable of conferring long-lasting immunity from birth. Recently, a live, attenuated whooping cough vaccine, BPZE1, has been developed. Here, an established murine immunization model was used to examine the induction and longevity of immunological memory. In this predictive model, BPZE1 conferred a level of protection against virulent bacterial challenge comparable to that conferred by recovery from prior infection, up to 1 year after immunization. One year after immunization with BPZE1, a pertussis-specific persistent response, with high levels of gamma interferon (IFN-γ), could be detected from spleen cells restimulated with inactivated Bordetella pertussis. BPZE1 induced low levels of interleukin-17 (IL-17) and no IL-10 or IL-5. BPZE1 immunization induced long-lasting, efficacious memory B-cell and specific antibody responses dominated by IgG2a, which were boosted by subsequent challenge. Finally, the antibody induced by BPZE1 was functionally relevant and could clear a virulent B. pertussis infection in antibody-deficient mice following passive transfer. This study suggests that BPZE1 is capable of conferring a high level of long-lived effective protection against virulent B. pertussis.
authors.affiliation: Institute of Immunology, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland.
authors.forename: Ciaran M
authors.initials: CM
authors.lastname: Skerry
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Mahon
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D058491:Bacterial Load; D001886:Bordetella pertussis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010567:Pertussis Vaccine / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007378:Interleukins; D010567:Pertussis Vaccine; D014613:Vaccines, Attenuated; D007371:Interferon-gamma