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

Autor(es):Mostrar menos -

Castro, Julia T. ^[1] ; Oliveira, Giuliana S. ^[1] ; Nishigasako, Melissa A. ^[1] ; Debrie, Anne-Sophie ^[2] ; Miyaji, Eliane N. ^[1] ; Soares-Schanoski, Alessandra ^[1] ; Akamatsu, Milena A. ^[3] ; Locht, Camille ^[2] ; Ho, Paulo L. ^[3] ; Mielcarek, Nathalie ^[2] ; Oliveira, Maria Leonor S. ^[1]

Afiliação do(s) autor(es)

^[1] Inst Butantan, Lab Bacteriol, Sao Paulo, SP - Brazil

^[2] Univ Lille, Inst Pasteur Lille, CIIL Ctr Infect & Immun Lille, CNRS, INSERM, CHU Lille, U1019, UMR 8204, Lille - France

^[3] Inst Butantan, Secao Vacinas Aerob, Div Bioind, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 15, n. 1 JAN 16 2020.
• Citações Web of Science: 1

Resumo

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 wP(PspA4Pro). Subcutaneous immunization of mice with wP(PspA4Pro) induced low levels of anti-PspA4 IgG, even after 3 doses, and did not protect against a lethal pneumococcal challenge. Prime-boost strategies using wP(PspA4Pro) and PspA4Pro showed that there was no advantage in using the wP(PspA4Pro) 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-PspA4-Pro IgG, but no protection, suggesting that the antibodies induced by the fusion protein were not directed to protective epitopes. (AU)

• Processo FAPESP: 16/17258-9 - Bordetella pertussis e seus componentes como sistemas de entrega e adjuvantes para o desenvolvimento de vacinas contra Streptococcus pneumoniae
• Beneficiário: Júlia Tavares de Castro
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/01992-8 - Ação adjuvante da Hemaglutinina filamentosa (FHA) de Bordetella pertussis em fusão com o antígeno PspA de Streptococcus pneumoniae
• Beneficiário: Melissa Akemi Nishigasako
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 16/13134-3 - Vacinas recombinantes contra Streptococcus pneumoniae e Bordetella pertussis
• Beneficiário: Maria Leonor Sarno de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular