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

PLoS One. 2020 Jan 16;15(1):e0228055. doi: 10.1371/journal.pone.0228055. eCollection 2020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / administration & dosage*
  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antigens, Bacterial / pharmacology
  • Antigens, Surface / pharmacology
  • Bacterial Proteins / pharmacology*
  • Drug Carriers / administration & dosage
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Pertussis Vaccine / administration & dosage*
  • Pneumococcal Infections / prevention & control*
  • Vaccination
  • Virulence Factors, Bordetella / administration & dosage*

Substances

  • Adhesins, Bacterial
  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Antigens, Surface
  • Bacterial Proteins
  • Drug Carriers
  • Pertussis Vaccine
  • Virulence Factors, Bordetella
  • filamentous hemagglutinin adhesin, Bordetella pertussis
  • pneumococcal surface protein A

Grants and funding

This work was supported by FAPESP (grant 2016/13134-3), CNPq (301856/2016-8) and Fundação Butantan. Castro JT received a PhD fellowship and Nishigasako MA received an undergraduate fellowship (FAPESP 2016/17258-9 and 2017/01992-8); Oliveira GS received a Msc fellowship from CAPES, Brasil. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.