title: Human antibodies to PhtD, PcpA, and Ply reduce adherence to human lung epithelial cells and murine nasopharyngeal colonization by Streptococcus pneumoniae.
abstract: Streptococcus pneumoniae adherence to human epithelial cells (HECs) is the first step in pathogenesis leading to infections. We sought to determine the role of human antibodies against S. pneumoniae protein vaccine candidates PhtD, PcpA, and Ply in preventing adherence to lung HECs in vitro and mouse nasopharyngeal (NP) colonization in vivo. Human anti-PhtD, -PcpA, and -Ply antibodies were purified and Fab fragments generated. Fabs were used to test inhibition of adherence of TIGR4 and nonencapsulated strain RX1 to A549 lung HECs. The roles of individual proteins in adherence were tested using isogenic mutants of strain TIGR4. Anti-PhtD, -PcpA, and -Ply human antibodies were assessed for their ability to inhibit NP colonization in vivo by passive transfer of human antibody in a murine model. Human antibodies generated against PhtD and PcpA caused a decrease in adherence to A549 cells (P < 0.05). Anti-PhtD but not anti-PcpA antibodies showed a protective role against mouse NP colonization. To our surprise, anti-Ply antibodies also caused a significant (P < 0.05) reduction in S. pneumoniae colonization. Our results support the potential of PhtD, PcpA, and Ply protein vaccine candidates as alternatives to conjugate vaccines to prevent non-serotype-specific S. pneumoniae colonization and invasive infection.
authors.affiliation: Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester, New York, USA.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Kaur
authors.affiliation: Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester, New York, USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Surendran
authors.affiliation: Sanofi Pasteur, Lyon, France.
authors.forename: Martina
authors.initials: M
authors.lastname: Ochs
authors.affiliation: Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester, New York, USA michael.pichichero@rochestergeneral.org.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pichichero
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002353:Carrier State / Q000517:prevention & control; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D047908:Intracellular Signaling Peptides and Proteins; D008810:Mice, Inbred C57BL; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000502:physiology; D013301:Streptolysins / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C113653:PcpA protein, Streptococcus; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae