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咨询顾问3D-PHAD®
Monophosphoryl 3-Deacyl Lipid A (Synthetic)Pat No. 9,241,988
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 highly pure MPLA analog, 3D-PHAD®, provides a homogeneous synthetic equivalent for the 3-deacylated MPLA derived from bacterial LPS. While comparable to bacterial MPLA and other synthetic MPLA analogs at eliciting an immune response in a liposomal adjuvant system (see bar graph), 3D-PHAD® is less pyrogenic than its bacterial-derived mimic. Extensive preclinical testing with 3D-PHAD® demonstrated equivalency to PHAD®, and human trials have been scheduled for launch. 3D-PHAD® is protected under Pat No. 9,241,988. Licensing opportunities are available for vaccine or immunotherapy commercialization.
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).
