Liposomal oral DNA vaccine (mycobacterium DNA) elicits immune response.
Tuberculosis is one of the leading causes of mortality from an infectious disease worldwide, however, the efficacy of BCG vaccine against adult pulmonary tuberculosis still remains instability. Therefore, it is an urgent work to develop both safe and effective vaccine to TB. To clarify the liposome encapsulated DNA vaccine was effectively working as a vaccine delivery system to evoke mucosal intestinal immune responses. A Mycobacterium pcDNA3.1(+)/Ag85A DNA was constructed and encapsulated into liposome. Ag85A protein antigen was observed to substantially express in the epithelium, microfold cells (M cells), dendritic cells (DCs) and Peyer's patches (pp) of the small intestine, respectively, after oral administration into C57BL/6 mice 3 times each 14 days interval. Furthermore, levels of IL-2 and IFN-gamma in the IELs isolated from the small intestine were markedly increased, IL-4 level was not significantly changed as compared to those in control group after oral administration of Ag85A DNA encapsulated in liposome, together with the augmented Ag85A-specific cytotoxicity of IELs, indicating a local Th1 dominant cellular immune response was elicited, and thus enhanced cytotoxicity of IELs as compared to those in control mice. Furthermore, sIgA level was also elevated in liposomal encapsulated Ag85A DNA immunized mice. These data indicated that oral vaccination with the liposomal-pcDNA 3.1(+)/Ag85A DNA is able to induce antigen specific mucosal cellular and humoral immune responses. Especially, cellular compartment in the epithelium of small intestine plays a key role on the regulation of immune response to eliminate TB. These findings have important understanding and possible implications for the design of new strategies based on oral DNA vaccine on regulation of immune response in protection against TB. Further study is clearly necessary to improve the effectiveness of Ag85A DNA vaccines against TB as compared with BCG.
Wang
Danan
D
Department of Immunology, China Medical University, 92, North Second Road, Heping District, Shenyang 110001, China.
Xu
Jia
J
Feng
Yonghui
Y
Liu
Ying
Y
Mchenga
S S Salum
SS
Shan
Fengping
F
Sasaki
Jin-ichi
J
Lu
Changlong
C
D000217:Acyltransferases / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D005260:Female; D007071:Immunoglobulin A, Secretory / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007071:Immunoglobulin A, Secretory; D007376:Interleukin-2; D008081:Liposomes; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis