Yields and Immunomodulatory Effects of Pneumococcal Membrane Vesicles Differ with the Bacterial Growth Phase

Mina Mehanny1,2,3, Tobias Kroniger4, Marcus Koch5

  • 1Helmholtz Institute for Pharmaceutical Research Saarland, Biogenic Nanotherapeutics Group, Campus E8.1, Saarbrücken, 66123, Germany.

Insights

Bacterial membrane vesicles (MVs) from Streptococcus pneumoniae show potential as vaccine candidates. While death-phase MVs offer higher yields, stationary-phase MVs are equally effective due to similar immunogenic proteins and uptake.

Area of Science:

  • Microbiology
  • Immunology
  • Vaccine Development

Background:

  • Streptococcus pneumoniae infections cause significant global mortality.
  • Bacterial membrane vesicles (MVs) are explored as vaccine candidates due to their antigenic properties.
  • Pneumococcal MVs require high yield and immunogenicity without compromising immune cell viability for clinical use.

Purpose of the Study:

  • To compare the yield, immunogenicity, and cytotoxicity of MVs isolated from stationary-phase (24h) and death-phase (48h) cultures of Streptococcus pneumoniae.
  • To evaluate the potential of these MVs as vaccine candidates.

Main Methods:

  • Isolation of MVs from stationary and death phases of bacterial growth.
  • Assessment of MV yield, cytotoxicity in cell lines and primary human macrophages/dendritic cells.
  • Analysis of cytokine release (TNF-α, IL-6) from immune cells upon MV exposure.
  • Proteomic analysis of MVs to identify key immunogenic proteins.

Main Results:

  • Death-phase MVs exhibited higher yields than stationary-phase MVs.
  • Both MV types demonstrated acceptable compatibility with immune cells and cell lines.
  • Comparable uptake and enhanced inflammatory cytokine release (TNF-α, IL-6) were observed for both MV types.
  • Proteomic analysis revealed similar key antigenic proteins (e.g., pneumolysin, PspA) but lower autolysin levels in stationary-phase MVs.

Conclusions:

  • Despite higher yields, death-phase MVs did not show superiority over stationary-phase MVs as vaccine candidates.
  • Similar antigenic protein composition and immune cell uptake contribute to comparable efficacy.
  • Stationary-phase MVs may be preferable due to lower autolysin levels, warranting further investigation.