Enhancement of humoral immune responses against viral vaccines by a non-pyrogenic 6-O-acylmuramyldipeptide and synthetic low toxicity analogues of lipid A.
6-O-Acyl derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and synthetic, low toxicity lipid-A analogues were examined for their ability to enhance the potency of current viral vaccines. 6-O-(2-Tetradecylhexadecanoyl)-MDP (B30-MDP) in non-irritative vehicles such as physiological saline, phosphate-buffered saline (PBS), squalene-PBS emulsion, Intralipid or liposomes, significantly stimulated the primary and secondary antibody production of guinea-pigs against influenza split or subunit vaccine and inactivated the hepatitis B virus surface (HBs) antigen. Mice seemed less responsive to the adjuvanticity of B30-MDP than guinea-pigs. Two low toxicity lipid A analogues, acylated beta(1-6)-D-glucosamine disaccharide bisphosphates (which do not have amide-bound or ester-bound 3-acyloxyacyl groups unlike fully toxic Escherichia coli-type lipid A), caused significantly enhanced antibody responses, primary or secondary, when administered to mice by incorporation into liposomes with inactivated HBs antigen.
Tsujimoto
M
M
Department of Microbiology and Oral Microbiology, Osaka University Dental School, Japan.
Kotani
S
S
Okunaga
T
T
Kubo
T
T
Takada
H
H
Kubo
T
T
Shiba
T
T
Kusumoto
S
S
Takahashi
T
T
Goto
Y
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006168:Guinea Pigs; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D007252:Influenza Vaccines; D008050:Lipid A / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009975:Orthomyxoviridae / Q000276:immunology; D013997:Time Factors; D014765:Viral Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006514:Hepatitis B Surface Antigens; D007252:Influenza Vaccines; D008050:Lipid A; D014765:Viral Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C044706:B 30-muramyl dipeptide