title: Pneumococcal pep27 mutant immunization stimulates cytokine secretion and confers long-term immunity with a wide range of protection, including against non-typeable strains.
abstract: Streptococcus pneumoniae is comprised of more than 90 serotypes and is the major causative agent of pneumonia, which results in over 1million 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 3months 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.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Gyu-Lee
authors.initials: GL
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seung-Han
authors.initials: SH
authors.lastname: Seon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seungyeop
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Sang-Sang
authors.initials: SS
authors.lastname: Park
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Seoul 152-703, Republic of Korea.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: dkrhee@skku.edu.
authors.forename: Dong-Kwon
authors.initials: DK
authors.lastname: Rhee
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002353:Carrier State / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines
keywords: Broad-spectrum protection; Mucosal immunity; Streptococcus pneumoniae; pep27 mutant