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Synthesis and delivery of Streptococcus pneumoniae capsular polysaccharides by recombinant attenuated Salmonella

Huali Su1,2, Qing Liu1, Xiaoping Bian1

  • 1College of Veterinary Medicine, Southwest University, Chongqing 400715, China.

Proceedings of the National Academy of Sciences of the United States of America
|December 31, 2020
PubMed

Insights

This study developed a low-cost live vaccine using recombinant attenuated Salmonella vaccine strains to express Streptococcus pneumoniae capsular polysaccharides. This innovative approach offers a promising strategy for global pneumococcal disease prevention.

Area of Science:

  • Microbiology
  • Immunology
  • Vaccinology

Background:

  • Streptococcus pneumoniae capsular polysaccharides (CPSs) are key virulence factors and targets of current pneumococcal vaccines.
  • Existing polysaccharide-based vaccines are costly and difficult to produce, limiting their global accessibility.
  • There is a need for affordable and effective pneumococcal vaccines, especially for developing countries.

Purpose of the Study:

  • To develop a low-cost live vaccine against Streptococcus pneumoniae using a recombinant attenuated Salmonella vaccine (RASV) system.
  • To express seven different serotypes of S. pneumoniae CPSs in RASV strains.
  • To evaluate the immunogenicity and protective efficacy of the developed RASV-CPS vaccine in a mouse model.

Main Methods:

  • Genes encoding seven different S. pneumoniae CPS serotypes were cloned and expressed in an RASV strain.
  • Mice were orally immunized with the developed RASV-CPS strains.
  • Immune responses, including Th1-biased adaptive immunity and CPS-specific antibody production, were analyzed.
  • Opsonophagocytic killing assays were performed in vitro.
  • Mice were challenged with virulent S. pneumoniae strains to assess vaccine protection.

Main Results:

  • Oral immunization with RASV-CPS strains induced robust Th1-biased adaptive immune responses in mice.
  • CPS-specific antisera demonstrated opsonophagocytic killing activity against corresponding S. pneumoniae serotypes in vitro.
  • RASV-CPS2 and RASV-CPS3 strains provided significant protection against challenge infections with S. pneumoniae strains D39 and WU2.
  • The RASV system successfully synthesized and delivered S. pneumoniae CPSs.

Conclusions:

  • The synthesis and delivery of S. pneumoniae CPSs using RASV strains represent an innovative strategy for developing low-cost pneumococcal vaccines.
  • This approach holds potential for improved vaccine production and accessibility worldwide.
  • The RASV-CPS vaccine platform shows promise for future pneumococcal disease prevention efforts.

Keywords:
Streptococcus pneumoniaecapsular polysaccharidespneumococcal vaccinerecombinant attenuated Salmonella vaccine

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