Enhancement of immunoglobulin G responses in mice against hepatitis B virus surface antigen, influenza virus hemagglutinin vaccine, and tetanus toxoid by 6-O-acylated muramyl dipeptides.
The adjuvant activity of chemically synthesized 6-O-acylated muramyl dipeptides (MDP) was tested in aqueous form. The activity was assessed by determining immunoglobulin G (IgG) titers in sera of mice immunized with hepatitis B virus surface antigen, influenza virus hemagglutinin (HA) vaccine, or tetanus toxoid with an enzyme-linked immunosorbent assay. Administration of 6-O-acyl-MDP analogs with antigens induced marked enhancement of primary and secondary IgG antibody responses and maintained high antibody levels for at least 7 weeks. Among the analogs tested, an MDP methyl ester carrying a 6-O-3-hexadecanoyl-oxytetradecanoyl group (compound 309) exhibited the most intensive adjuvant activity. Its activity was stronger than that of 6-O-2-tetradecylhexadecanoyl (B3O)-MDP used as a positive control. However, accumulation of peritoneal cells and activation of peritoneal macrophages by compound 309 was weaker than that by 6-O-B30-MDP, suggesting that 309 as an immunoadjuvant is more suitable for vaccination in terms of its stronger enhancement of antibody formation and lower induction of inflammatory response than 6-O-B30-MDP.
Furuya
T
T
School of Hygienic Sciences, Kitasato University, Sagamihara, Japan.
Kumazawa
Y
Y
Takimoto
H
H
Nagumo
T
T
Watanabe
M
M
Aizawa
C
C
Kiso
M
M
Hasegawa
A
A
Nomoto
K
K
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000914:Antibodies, Viral / Q000096:biosynthesis*; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007252:Influenza Vaccines / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D010529:Peritoneal Cavity / Q000276:immunology / Q000502:physiology; D013745:Tetanus Toxoid / Q000276:immunology*
D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D013745:Tetanus Toxoid; D000119:Acetylmuramyl-Alanyl-Isoglutamine