Streptococcus pneumoniae, more than 90 serotypes of which exist, is recognized as an etiologic agent of pneumonia, meningitis, and sepsis associated with significant morbidity and mortality worldwide. Immunization with a pneumococcal pep27 mutant (Δpep27) has been shown to confer comprehensive, long-term protection against even non-typeable strains. However, Δpep27 is only effective as a vaccine after at least 3 rounds of immunization. Therefore, treatments capable of enhancing the efficiency of Δpep27 immunization should be identified without delay.