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Front. Immunol. | doi: 10.3389/fimmu.2019.01212

Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine with lgt Deletion

  • 1Korea Atomic Energy Research Institute (KAERI), South Korea
  • 2Seoul National University, South Korea
  • 3Lanzhou Veterinary Research Institute (CAAS), China
  • 4College of Medicine, Korea University, South Korea
  • 5College of Medicine, Ewha Womans University, South Korea

Streptococcus pneumoniae is the most common respiratory bacterial pathogen among cases of community-acquired infection in young children, older adults, and individuals with underlying medical conditions. Although capsular polysaccharide-based pneumococcal vaccines have contributed to significant decrease in invasive pneumococcal infections, these vaccines have some limitations, including limited serotype coverage, lack of effective mucosal antibody responses, and high costs. In this study, we investigated the safety and immunogenicity of a live, whole-cell pneumococcal vaccine constructed by deleting the gene for prolipoprotein diacylglyceryl transferase (lgt) from the encapsulated pneumococcal strain TIGR4 (TIGR4lgt) for protection against heterologous pneumococcal strains. Pneumococcal strain TIGR4 was successfully attenuated by deletion of lgt, resulting in the loss of inflammatory activity and virulence. TIGR4Δlgt colonized the nasopharynx long enough to induce strong mucosal IgA and IgG2b-dominant systemic antibody responses that were cross-reactive to heterologous pneumococcal serotypes. Finally, intranasal immunization with TIGR4Δlgt provided serotype-independent protection against pneumococcal challenge in mice. Taken together, our results suggest that TIGR4Δlgt is an avirulent and attractive broad-spectrum pneumococcal vaccine candidate. More broadly, we assert that modulation of such “master” metabolic genes represents an emerging strategy for developing more effective vaccines against numerous infectious agents.

Keywords: Streptococcus pneumoniae, LGT, lipoprotein, live attenuated vaccine, mucosal immunity

Received: 14 Jan 2019; Accepted: 13 May 2019.

Edited by:

Rajko Reljic, St George's, University of London, United Kingdom

Reviewed by:

Pietro Speziale, Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy
Simon M. Cutting, Royal Holloway, University of London, United Kingdom  

Copyright: © 2019 Jang, Ahn, Zhi, Ji, Zhang, Han, Guo, Lim, Song, Lim and Seo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Jae Hyang Lim, College of Medicine, Ewha Womans University, Seoul, 03760, South Korea, jlim19@ewha.ac.kr
Dr. Ho Seong Seo, Korea Atomic Energy Research Institute (KAERI), Daejeon, South Korea, hoseongseo@kaeri.re.kr