Colonization by Streptococcus pneumoniae

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 pre-venting 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 nonen-capsulated 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 colo-nization. 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. Streptococcus pneumoniae is an important human pathogen thatcolonizes the nasopharynx (NP) and causes local (acute otitis media [AOM] and sinusitis) and severe (pneumonia, sepsis, and meningitis) invasive infections (1–3). Adherence of S. pneumoniae to NP epithelial cells is a first step in its pathogenesis, and its attachment to lung epithelial cells is required to establish pneu