Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 23, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2122386119
Keywords
Streptococcus pneumoniae; pneumococci; serotype-independent vaccine; membrane particles; membrane vesicles
Categories
Funding
- Family Erling Persson Foundation
- Swedish Foundation for Strategic Research
- Swedish Research Council
- Stockholm County Council
- Torsten Soderberg foundation
- Knut and Alice Wallenberg Foundation
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Intranasal immunization with pneumococcal membrane particles (MPs) provides excellent serotype-independent protection against invasive pneumococcal disease (IPD). The conserved lipoproteins MalX and PrsA are identified as the main antigens responsible for cross-protection. Omitting variable surface proteins and vaccine candidate PspA enhances protective immune responses to the conserved proteins.
Pneumococcal conjugate vaccines (PCVs) used in childhood vaccination programs have resulted in replacement of vaccine-type with nonvaccine-type pneumococci in carriage and invasive pneumococcal disease (IPD). A vaccine based on highly conserved and protective pneumococcal antigens is urgently needed. Here, we performed intranasal immunization of mice with pneumococcal membrane particles (MPs) to mimic natural nasopharyngeal immunization. MP immunization gave excellent serotype-independent protection against IPD that was antibody dependent but independent of the cytotoxin pneumolysin. Using Western blotting, immunoprecipitation, mass spectrometry, and different bacterial mutants, we identified the conserved lipoproteins MalX and PrsA as the main antigens responsible for cross-protection. Additionally, we found that omitting the variable surface protein and vaccine candidate PspA from MPs enhanced protective immune responses to the conserved proteins. Our findings suggest that MPs containing MalX and PrsA could serve as a platform for pneumococcal vaccine development targeting the elderly and immunocompromised.
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