1. Evaluation of inactivated Bordetella pertussis as a delivery system for the immunization of mice with Pneumococcal Surface Antigen A.
- Author
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Castro JT, Oliveira GS, Nishigasako MA, Debrie AS, Miyaji EN, Soares-Schanoski A, Akamatsu MA, Locht C, Ho PL, Mielcarek N, and Oliveira MLS
- Subjects
- Animals, Antigens, Bacterial pharmacology, Antigens, Surface pharmacology, Drug Carriers administration & dosage, Female, Mice, Mice, Inbred BALB C, Vaccination, Adhesins, Bacterial administration & dosage, Adjuvants, Immunologic administration & dosage, Bacterial Proteins pharmacology, Pertussis Vaccine administration & dosage, Pneumococcal Infections prevention & control, Virulence Factors, Bordetella administration & dosage
- Abstract
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., Competing Interests: ML Oliveira, EN Miyaji and PL Ho have a patent deposit for the use of the whole cell pertussis vaccine as adjuvant to PspA in Brazil (INPI PI 1003753-5 A2). This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2020
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