Evaluation of inactivated Bordetella pertussis as a delivery system for the immunization of mice with Pneumococcal Surface Antigen A

Autoři: Julia T. Castro aff001;  Giuliana S. Oliveira aff001;  Melissa A. Nishigasako aff001;  Anne-Sophie Debrie aff002;  Eliane N. Miyaji aff001;  Alessandra Soares-Schanoski aff001;  Milena A. Akamatsu aff003;  Camille Locht aff002;  Paulo L. Ho aff003;  Nathalie Mielcarek aff002;  Maria Leonor S. Oliveira aff001
Působiště autorů: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil aff001;  Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 –UMR 8204 –CIIL—Center for Infection and Immunity of Lille, Lille, France aff002;  Seção de Vacinas Aeróbicas, Divisão Bioindustrial, Instituto Butantan, São Paulo, SP, Brazil aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0228055


Pneumococcal Surface Protein A (PspA) has been successfully tested as vaccine candidate against Streptococcus pneumoniae infections. Vaccines able to induce PspA-specific antibodies and Th1 cytokines usually provide protection in mice. We have shown that the whole cell pertussis vaccine (wP) or components from acellular pertussis vaccines, such as Pertussis Toxin or Filamentous Hemagglutinin (FHA), are good adjuvants to PspA, suggesting that combined pertussis-PspA vaccines would be interesting strategies against the two infections. Here, we evaluated the potential of wP as a delivery vector to PspA. Bordetella pertussis strains producing a PspA from clade 4 (PspA4Pro) fused to the N-terminal region of FHA (Fha44) were constructed and inactivated with formaldehyde for the production of wPPspA4Pro. Subcutaneous immunization of mice with wPPspA4Pro induced low levels of anti-PspA4 IgG, even after 3 doses, and did not protect against a lethal pneumococcal challenge. Prime-boost strategies using wPPspA4Pro and PspA4Pro showed that there was no advantage in using the wPPspA4Pro vaccine. Immunization of mice with purified PspA4Pro induced higher levels of antibodies and protection against pneumococcal infection than the prime-boost strategies. Finally, purified Fha44:PspA4Pro induced high levels of anti-PspA4Pro IgG, but no protection, suggesting that the antibodies induced by the fusion protein were not directed to protective epitopes.

Klíčová slova:

Antibodies – Bordetella pertussis – Cloning – Enzyme-linked immunoassays – Pneumococcus – Recombinant proteins – Recombinant vaccines – Vaccines


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