title: Effect of cationic liposomes on BCG trafficking and vaccine-induced immune responses following a subcutaneous immunization in mice.
abstract: While formulating Mycobacterium bovis BCG in lipid-based adjuvants has been shown to increase the vaccine's protective immunity, the biological mechanisms responsible for the enhanced potency of lipid encapsulated BCG are unknown. To assess whether mixing BCG in adjuvant increases its immunogenicity by altering post-vaccination organ distribution and persistence, mice were immunized subcutaneously with conventional BCG Pasteur or BCG formulated in DDA/TDB adjuvant and the bio-distribution of BCG bacilli was evaluated in mouse lungs, spleens, lymph nodes, and livers for up to 1 year. Although BCG was rarely detected in mouse livers, mycobacteria were found in mouse lungs, spleens, and lymph nodes for at least 1 year post-vaccination. However, at various time points during the 1 year study, the frequency of lung and spleen infections and the number of mycobacteria in infected organs of individual mice were highly variable. In contrast, mycobacteria were nearly always detected in the lymph nodes of vaccinated mice. While the frequency and extent of lymph node infections generally were not significantly different between mice vaccinated with adjuvanted or nonadjuvanted BCG preparations, multiparameter flow cytometry analysis of lymph node cells showed significantly higher frequencies of CD4+ and CD8+ T cells expressing IFN-γ and IFN-γ/TNF-α in mice immunized with adjuvanted BCG. Overall, our data suggest that the relationship between lymph node infection and the generation of anti-tuberculosis protective responses following BCG vaccination should be further investigated.
authors.affiliation: Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Silver Spring, MD 20993, United States. Electronic address: steven.derrick@fda.hhs.gov.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Derrick
authors.affiliation: Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Silver Spring, MD 20993, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Yang
authors.affiliation: Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Silver Spring, MD 20993, United States.
authors.forename: Marcela
authors.initials: M
authors.lastname: Parra
authors.affiliation: Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, United States.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Kolibab
authors.affiliation: Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Silver Spring, MD 20993, United States.
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Morris
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D008081:Liposomes / Q000008:administration & dosage*; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000302:isolation & purification; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Adjuvants; BCG; Immunity; Tuberculosis