title: Improved protection against tuberculosis after boosting the BCG-primed mice with subunit Ag 85a delivered through intact skin with deformable vesicles.
abstract: To improve vaccination against tuberculosis (TBC) with Bacillus Calmette-Guerin (BCG), we introduce novel, non-invasive, secondary immunisations relying on epicutaneous (e.c.) applications of the TBC subunit antigen, Ag 85a, associated with deformable carrier vesicles. Immuno-boosting with such antigen-vesicles recruits more CD11c positive cells into the draining murine lymph nodes, and typically stimulates, especially the proximal, immune cells more than immunogen injections. Non-invasive antigen application also protects mice better against an infection with TBC. Subcutaneous injections of vesicular Ag 85a into BCG-primed mice mainly yield IgG1 and IgG2a, indicative of a mixed Th1 and Th2 response. Conversely, transcutaneous immuno-boosts of such mice with a deformable vesicle-Ag 85a combination mainly generate serum IgA and IgG2a, indicative of an IgA facilitated, Th1-mediated, immune response. The Ag 85a specific antibody titres are generally low, but T lymphocytes also proliferate in the immunised mice. The new, partially non-invasive, vaccination method lowers the burden of pulmonary infection with M. tuberculosis. In mice immunised with Ag85a associated with deformable vesicles we measured 116× (e.c.) to 51× (s.c.) lower colony forming units number in spleen and 9× (e.c.) to 3× (s.c.) lower such number in lungs.
authors.affiliation: Dayalbagh Educational Institute, Dayalbagh, Agra 282 005, India.
authors.forename: Gavish
authors.initials: G
authors.lastname: Kumar
authors.affiliation: Dayalbagh Educational Institute, Dayalbagh, Agra 282 005, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Sharma
authors.affiliation: National JALMA Institute for Leprosy & Other Mycobacterial Diseases, Tajganj, Agra, India.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Gupta
authors.affiliation: National JALMA Institute for Leprosy & Other Mycobacterial Diseases, Tajganj, Agra, India.
authors.forename: Beenu
authors.initials: B
authors.lastname: Joshi
authors.affiliation: National JALMA Institute for Leprosy & Other Mycobacterial Diseases, Tajganj, Agra, India.
authors.forename: Umesh Datta
authors.initials: UD
authors.lastname: Gupta
authors.affiliation: The Advanced Treatments Institute, Tassilostr. 3, D-82131 Gauting, Germany, E. U.
authors.forename: Gregor
authors.initials: G
authors.lastname: Cevc
authors.affiliation: Dayalbagh Educational Institute, Dayalbagh, Agra 282 005, India. Electronic address: amla@dei.ac.in.
authors.forename: Amla
authors.initials: A
authors.lastname: Chopra
mesh_terms: D000217:Acyltransferases / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000279:Administration, Cutaneous; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D007114:Immunization / Q000379:methods; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008168:Lung / Q000382:microbiology; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis
keywords: Antibody isotype; Antibody titre; Antigen dermal presentation; Deformable vesicle; Immunisation against TBC; Non-invasive; Transcutaneous delivery