Pneumococcal pep27 mutant immunization stimulates cytokine secretion and confers long-term immunity with a wide range of protection, including against non-typeable strains

Streptococcus pneumoniae is comprised of more than 90 serotypes and is the major causative agent of pneumonia, which results in over 1 million deaths worldwide every year. Currently available injectable vaccines can protect against only 13-23 serotypes, and result in decrease of colonization against vaccine serotypes. However, they are neither effective for inhibition of non-vaccine serotypes colonization nor inhibition against initial colonization in the nasopharynx against various serotypes. Thus, development of a vaccine conveying broader protection at the colonization stage is required. This study examined whether the Δpep27 mutant could provide protection at the nasopharynx against a broad range of serotypes. Δpep27 immunization stimulated secretion of IL-4, IL-10, TNF-α, INF-γ and IL-17, and significantly increased secretory-IgA levels in bronchoalveolar lavage fluid. Colonization and opsonophagocytosis assays demonstrated that Δpep27 immunization could protect against many heterologous infections, including non-typeable strains, at the nasopharynx, and prompted efficient killing of heterologous strains, suggesting that Δpep27 immunization provides a wide range of cross-protection. Furthermore, Δpep27 immunization significantly increased both the survival rate and the level of IgG 3 months post-immunization, demonstrating long-lasting immunity. Thus, Δpep27 could serve as a highly feasible mucosal vaccine once it is further developed into a non-transformable strain.