Open AccessMucosal Vaccination with a Multivalent, Live-Attenuated Vaccine Induces Multifactorial Immunity against Pseudomonas aeruginosa Acute Lung Infection
Author(s) -
Akinobu Kamei,
Yamara S. Coutinho-Sledge,
Joanna B. Goldberg,
Gregory P. Priebe,
Gerald B. Pier
Publication year - 2011
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01139-10
Subject(s) - antigen , biology , immune system , antibody , vaccination , microbiology and biotechnology , immunity , immunology , pseudomonas aeruginosa , effector , immunization , attenuated vaccine , lipopolysaccharide , virology , active immunization , virulence , bacteria , biochemistry , genetics , gene
Many animal studies investigating adaptive immune effectors important for protection againstPseudomonas aeruginosa have implicated opsonic antibody to the antigenically variable lipopolysaccharide (LPS) O antigens as a primary effector. However, active and passive vaccination of humans against these antigens has not shown clinical efficacy. We hypothesized that optimal immunity would require inducing multiple immune effectors targeting multiple bacterial antigens. Therefore, we evaluated a multivalent live-attenuated mucosal vaccination strategy in a murine model of acuteP. aeruginosa pneumonia to assess the contributions to protective efficacy of various bacterial antigens and host immune effectors. Vaccines combining 3 or 4 attenuated strains having different LPS serogroups were associated with the highest protective efficacy compared to vaccines with fewer components. Levels of opsonophagocytic antibodies, which were directed not only to the LPS O antigens but also to the LPS core and surface proteins, correlated with protective immunity. The multivalent live-attenuated vaccines overcame prior problems involving immunologic interference in the development of O-antigen-specific antibody responses when closely related O antigens were combined in multivalent vaccines. Antibodies to the LPS core were associated within vitro killing andin vivo protection against strains with O antigens not expressed by the vaccine strains, whereas antibodies to the LPS core and surface proteins augmented the contribution of O-antigen-specific antibodies elicited by vaccine strains containing a homologous O antigen. Local CD4 T cells in the lung also contributed to vaccine-based protection when opsonophagocytic antibodies to the challenge strain were absent. Thus, multivalent live-attenuated vaccines elicit multifactorial protective immunity toP. aeruginosa lung infections.