3D(6-acyl) PHAD®
Monophosphoryl Hexa-acyl Lipid A, 3-Deacyl (Synthetic)
Vaccination is well-accepted as an effective method to prevent infections by mounting pathogen-specific immune responses prior to the infection. Usually, immunization with vaccine antigens alone is not able to induce robust or long-lasting immune responses — resulting in failure of protective immunity against infections. Thus, adjuvants are required to enhance cellular or humoral immune responses upon immunization. Because vaccine adjuvants using Lipid A have proven to be safe and effective in inducing Th-1 type immune responses to heterologous proteins in animal and human vaccines, Avanti developed Phosphorylated HexaAcyl Disaccharide (PHAD®), the first fully synthetic monophosphoryl Lipid A available for use as an adjuvant in human vaccines.
The MPLA structural analog, 3D(6-acyl)-PHAD® , is the synthetic MPLA most closely related to the reported structure of MPL® Adjuvant used in GSK’s Adjuvant Systems AS01, AS02, and AS04. As with other synthetic MPLA analogs manufactured by Avanti, it is structurally homogeneous and highly purified, and mimics the TLR4 agonist activity of bacterial MPLA.
Stimulatory effect of PHAD®, 3D-PHAD®, and 3D(6-acyl)-PHAD® on macrophages. Macrophage cell line J774 cells were cultured with Avanti PHAD®, 3D-PHAD®, or 3D(6-acyl)-PHAD® for 24hrs. IL-12 levels in supernatants were measured by sandwich ELISA.
Adjuvant Activity
PHAD®, 3D-PHAD®, and 3D(6A)-PHAD® have been tested extensively in animals using a variety of antigens. In all cases, these adjuvants exhibit a similar activity and safety profile to bacterially-derived MPL. The data above demonstrate the equivalency of the three synthetic adjuvants to the bacterially-derived MPL when presented in a liposomal carrier system (DMPC/DMPG/Cholesterol).