Membrane particles evoke a serotype-independent cross-protection

Pneumococcal infections are major contributors to morbidity and mortality worldwide. The introduction of pneumococcal conjugate vaccines (PCVs) into the childhood immunization program resulted in a decrease in invasive pneumococcal disease (IPI) in vaccinated children, but simultaneously an increase in non-vaccine IPI, also in age groups unvaccinated such as the elderly. Thus, new vaccine approaches are urgently needed, especially for the elderly, targeting all pneumococci responsible for IPD.

Here, we show that pneumococcal membrane (MP) particles evoke serotype-independent cross-protection against IPD. This protection is dependent on the presence of the two conserved lipoproteins MalX and PrsA. We suggest that MPs can be used for the development of pneumococcal vaccines.

Pneumococcal conjugate vaccines (PCVs) used in childhood immunization programs have resulted in replacement of vaccine-like pneumococci with non-vaccine pneumococci in carriers 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 (MP) particles to mimic natural immunization of the nasopharynx. Immunization against PD gave excellent serotype-independent protection against IPD which was antibody-dependent but independent of the cytotoxin pneumolysin.

Using Western blot, 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 omission of the MPS variable surface protein and vaccine candidate PspA enhanced protective immune responses against conserved proteins.

Our results suggest that MPs containing MalX and PrsA could serve as a platform for the development of pneumococcal vaccines targeting the elderly and immunocompromised.