699800 | MPLA (PHAD®)

Monophosphoryl Lipid A (Synthetic) (PHAD®)


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MPLA (PHAD®)

MPLA (PHAD®)

Monophosphoryl Lipid A (Synthetic) (PHAD®)

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.


PHAD® is a synthetic structural analog of monophosphoryl Lipid A (MPLA) that has been shown to boost the immune system through activation of the toll-like receptor 4 (TLR4) resulting in production of proinflammatory cytokines and antigen-specific effector CD4+ and memory CD8+ T cells. Also referred to as GLA, this adjuvant has been administered to well over 1000 human subjects without serious adverse events. PHAD® is available in bulk quantities for vaccine development and commercial manufacturing.


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

Antigen: gp140 from HIV-1












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).

Hygroscopic
No
Light Sensitive
No
Molecular Formula
C96H184N3O22P
Percent Composition
C 65.38%, H 10.52%, N 2.38% ,O 19.96%, P 1.76
Purity
> 99%
Stability
1 Years
Storage Temperature
-20°C
CAS Number
1246298-63-4
CAS Registry Number is a Registered Trademark of the American Chemical Society
Formula Weight
1763.469
Exact Mass
1762.311
Synonyms
PHAD®
phosphorylated hexaacyl disaccharide
Glycopyranoside Lipid A (GLA)

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PubMed ID: 32389496

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PubMed ID: 31827000

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PubMed ID: 31887349

Hernandez 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: 31567352

Maynard S, Marshall JD, MacGill RS, Yu L, Cann JA, Cheng LI, McCarthy MP, Cayatte C, Robbins SH. Vaccination with synthetic long peptide formulated with CpG in an oil-in-water emulsion induces robust E7-specific CD8 T cell responses and TC-1 tumor eradication. BMC Cancer. 2019 Jun 6;19(1):540. doi: 10.1186/s12885-019-5725-y.

PubMed ID: 31170937

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PubMed ID: 31075204

Liang T, Leung LM, Opene B, Fondrie WE, Lee YI, Chandler CE, Yoon SH, Doi Y, Ernst RK, Goodlett DR. Rapid microbial identification and antibiotic resistance detection by mass spectrometric analysis of membrane lipids. Anal Chem. 2018 Dec 20. doi: 10.1021/acs.analchem.8b02611. [Epub ahead of print]

PubMed ID: 30571097

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PubMed ID: 30522906

Jahan ST, Sadat SMA, Yarahmadi M, Haddadi A. Potentiating Antigen Specific Immune Response by Targeted Delivery of the PLGA-Based Model Cancer Vaccine. Mol Pharm. 2019 Feb 4;16(2):498-509. doi: 10.1021/acs.molpharmaceut.8b00700. Epub 2019 Jan 23.

PubMed ID: 30477303

Liang T, Leung LM, Opene B, Fondrie WE, Lee YI, Chandler CE, Yoon SH, Doi Y, Ernst RK, Goodlett DR. Rapid microbial identification and antibiotic resistance detection by mass spectrometric analysis of membrane lipids. Anal Chem. 2018 Dec 20. doi: 10.1021/acs.analchem.8b02611. [Epub ahead of print]

PubMed ID: 30571097

Lousada-Dietrich, S., Jogdand, P.S., Jepsen, S., Pinto, V.V., Ditlev, S.B., Christiansen, M., Larsen, S.O., Fox, C.B., Raman, V.S., Howard, R.F., Vedvick, T.S., Ireton, G., Carter, D., Reed, S.G., Theisen, M. (2011) A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2 - A GLURP-MSP3 fusion protein malaria vaccine candidate. Vaccine.

PubMed ID: 21349366

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PubMed ID: 21298114

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PubMed ID: 19748238

Coler, R.N., S.L. Baldwin, N. Shaverdian, S. Bertholet, S.J. Reed, V.S. Raman, X. Lu, J. DeVos, K. Hancock, J.M. Katz, T.S. Vedvick, M.S. Duthie, C.H. Clegg, N. Van Hoeven, and S.G. Reed. (2010). A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS One 5:e13677.

PubMed ID: 21060869

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PubMed ID: 20593273