Using procedure of emulsification-lyophilization to form lipid A-incorporating cochleates as an effective oral mucosal vaccine adjuvant-delivery system (VADS).
Using a procedure of emulsification-lyophilization (PEL), adjuvant lipid A-cochleates (LACs) were prepared as a carrier for model antigen bovine serum albumin (BSA). With phosphatidylserine and lipid A as emulsifiers dissolved in oil phase (O), sucrose and CaCl2 in the inner water phase (W1), and BSA, sucrose and PEG2000 in the outer water phase (W2), the W1/O/W2 emulsions were prepared and subsequently lyophilized to form a dry product which was stable enough to be stored at room temperature. Upon rehydration of the dry products, cochleates formed with a size of 800 nm and antigen association rates of 38%. After vaccination of mice through oral mucosal (o.m.) administration, LACs showed no side effects but induced potent immune responses as evidenced by high levels of IgG in the sera and IgA in the salivary, intestinal and vaginal secretions of mice. In addition, high levels of IgG2a and IFN-γ in the sera or culture supernatants of splenocytes of the immunized mice were also detected. These results revealed that LACs induced a mixed Th1/Th2 response against the loaded antigens. Thus, the LACs prepared by PEL were able to induce both systemic and mucosal immune responses and may act as a potent cold-chain-free oral mucosal vaccine adjuvant delivery system (VADS).
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, China.
Ning
N
Wang
Department of Pharmacy, Anhui Medical University, 81 Mei Hill Road, Hefei, Anhui Province 230032, China; Department of Pharmacy, Jining Medical College, 669 Xueyuan Road, Sunshine City, Shandong Province 276826, China. Electronic address: twangcn@hotmail.com.
Ting
T
Wang
Department of Pharmacy, Anhui Medical University, 81 Mei Hill Road, Hefei, Anhui Province 230032, China.
Meiling
M
Zhang
Department of Pharmacy, Anhui Medical University, 81 Mei Hill Road, Hefei, Anhui Province 230032, China.
Ruonan
R
Chen
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, China. Electronic address: pharmdeng@gmail.com.
Yihui
Y
Deng
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D005260:Female; D005612:Freeze Drying; D056724:Immunity, Humoral / Q000187:drug effects; D018928:Immunity, Mucosal / Q000187:drug effects*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D008050:Lipid A / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D051379:Mice; D009061:Mouth Mucosa / Q000187:drug effects* / Q000276:immunology; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D011208:Powders; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D013678:Technology, Pharmaceutical / Q000379:methods; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D008050:Lipid A; D011208:Powders; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma
Cochleate; Immune response; Lyophilization; Mucosa associated lymphoid tissue; Pathogen-associated molecular pattern; Vaccine adjuvant delivery system