699852 | 3D-PHAD®
Monophosphoryl 3-Deacyl Lipid A (Synthetic)Pat No. 9,241,988
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).
- ChemDraw File
- 3D Structure
- Structure
- Brochure
- 699852 Adjuvant Data
- Safety Data Sheet
Singh P, Matyas GR, Anderson A, Beck Z. Biophysical characterization of polydisperse liposomal adjuvant formulations. Biochem Biophys Res Commun. 2020 Aug 20;529(2):362-365. doi: 10.1016/j.bbrc.2020.05.156. Epub 2020 Jul 1. PMID: 32703436.
PubMed ID: 32703436Martin ML, Bitzer AA, Schrader A, Bergmann-Leitner ES, Soto K, Zou X, Beck Z, Matyas GR, Dutta S. Comparison of immunogenicity and safety outcomes of a malaria vaccine FMP013/ALFQ in rhesus macaques (Macaca mulatta) of Indian and Chinese origin. Malar J. 2019 Nov 27;18(1):377. doi: 10.1186/s12936-019-3014-5.
PubMed ID: 31775762Hernandez A, Luan L, Stothers CL, Patil NK, Fults JB, Fensterheim BA, Guo Y, Wang J, Sherwood ER, Bohannon JK. Phosphorylated Hexa-Acyl Disaccharides Augment Host Resistance Against Common Nosocomial Pathogens. Crit Care Med. 2019 Nov;47(11):e930-e938. doi: 10.1097/CCM.0000000000003967.
PubMed ID: 31567352Beugeling M, De Zee J, Woerdenbag HJ, Frijlink HW, Wilschut JC, Hinrichs WLJ. Respiratory syncytial virus subunit vaccines based on the viral envelope glycoproteins intended for pregnant women and the elderly. Expert Rev Vaccines. 2019 Sep;18(9):935-950. doi: 10.1080/14760584.2019.1657013. Epub 2019 Aug 25.
PubMed ID: 31446807Singh P, Bodycomb J, Travers B, Tatarkiewicz K, Travers S, Matyas GR, Beck Z. Particle size analyses of polydisperse liposome formulations with a novel multispectral advanced nanoparticle tracking technology. Int J Pharm. 2019 Jul 20;566:680-686. doi: 10.1016/j.ijpharm.2019.06.013. Epub 2019 Jun 6.
PubMed ID: 31176851Smith RJ, Bryant RG. Metal substitutions incarbonic anhydrase: a halide ion probe study. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1281-6.
PubMed ID: 31043512Cawlfield A, Genito CJ, Beck Z, Bergmann-Leitner ES, Bitzer AA, Soto K, Zou X, Hadiwidjojo SH, Gerbasi RV, Mullins AB, Noe A, Waters NC, Alving CR, Matyas GR, Dutta S. Safety, toxicity and immunogenicity of a malaria vaccine based on the circumsporozoite protein (FMP013) with the adjuvant army liposome formulation containing QS21 (ALFQ). Vaccine. 2019 Jun 27;37(29):3793-3803. doi: 10.1016/j.vaccine.2019.05.059. Epub 2019 May 28.
PubMed ID: 31151801Taleghani N, Bozorg A, Azimi A, Zamani H. Immunogenicity of HPV and HBV vaccines: adjuvanticity of synthetic analogs of monophosphoryl lipid A combined with aluminum hydroxide. APMIS. 2019 Mar;127(3):150-157. doi: 10.1111/apm.12927.
PubMed ID: 30746792- Certificate of Analysis(Lot No. 699852P-1MG-A-012and 5089PGA012)
- Certificate of Analysis(Lot No. 699852P-5MG-A-012and 5089PHA012)
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- Certificate of Analysis(Lot No. 699852P-5MG-B-012and 5089PHB012)
- Certificate of Analysis(Lot No. 699852P-1MG-B-013and 5089PGB013)
- Certificate of Analysis(Lot No. 699852P-5MG-A-013and 5089PHA013)
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- Certificate of Analysis(Lot No. 699852P-5MG-H-013and 5089PHH013)
