Lipid-based mRNA Vaccine

Lipid-based mRNA Vaccine Development Services

Creative Biolabs| Lipid-based mRNA Vaccine

Contents • Background • Lipid-based mRNA vaccines • Clinical progress on Lipid-based mRNA vaccines • Vaccine Formulation Development Service • Vaccine Analytics & Assessment Service • About Us • Contact

Creative Biolabs| Lipid-based mRNA Vaccine

Background Vaccine is a special biological preparation administered to healthy individuals

with the ability to stimulate immunity and protect the human body from infections and diseases. Conventional vaccine approaches such as inactivated pathogens and subunit vaccines and have prevented the spread of dozens of diseases. Along with the worldwide explosion of COVID-19 in 2020, a new vaccine platform, mRNA vaccine showed advantages of rapid development and scalable manufacture, which has been approved by FDA in early December, 2020 (BNT 162b2, Pfizer/BioNTech). Besides, mRNA vaccines can be more stable, at the same time, highly translatable through various modifications, allowing rapid cellular uptake and efficient expression. As mRNA is a noninfectious, non-integrating platform, there is no potential risk of infection or insertional mutagenesis which realizing higher safety of the mRNA vaccines.

In the past few years, lipid-based mRNA vaccine delivery has become one of the most appealing and commonly-used strategies.

The lipid components could provide protection for mRNA and improve transfection efficiency. As an expert in lipid-based drug delivery, Creative Biolabs is dedicated to improve human health and has successfully established in both drug delivery platforms and pre-clinical vaccine platforms. We have absolute advantages in novel mRNA vaccine development.

Creative Biolabs| Lipid-based mRNA Vaccine

Lipid-based mRNA Vaccines

The core principle behind mRNA as a technology for vaccination is to deliver the transcript of interest, encoding one or more immunogen(s) into the host cell cytoplasm where expression generates translated protein(s) are ultimately located in the membrane, to be secreted, or intracellular. Two categories of mRNA constructs are being evaluated: non-replicating mRNA (NRM) and self-amplifying mRNA (SAM). The workflow of mRNA vaccine contains: ① mRNA construction ② Cationic lipid encapsulation ③ Delivery & cellular uptake ④ Protein expression ⑤ Protein presentation & Immune response

Creative Biolabs| Lipid-based mRNA Vaccine

Lipid-based mRNA Vaccines Lipid Nanoparticles (LNPs) for delivery of mRNA vaccines LNPs consist of four main components: •

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Ionizable cationic lipid for absorption of electronegative mRNA and endosomal release of mRNA to the cytoplasm.

Lipid-linked polyethylene glycol (PEG) for particle size control and stability improvement.

Cholesterol, stabilizing agent.

Naturally occurring phospholipids for stabilization of lipid bilayer structure.

Creative Biolabs| Lipid-based mRNA Vaccine

Clinical Progress on Lipid-based mRNA Vaccines Name BioNTech Lipo-MERIT

Vehicle

Liposome-complexed TAA mRNA (i.v.)

Targets

Reference

Melanoma

NCT02410733

BioNTech TNBC-MERIT

Liposome-formulated TAA and neo-Ag mRNA (i.v.)

Breast cancer

NCT02316457

BioNTech PRO-MERIT

Liposome

PCA

NCT04382898

Moderna mRNA-1893

LNP

Zika virus

NCT03014089

Moderna mRNA-4157

LNP

Solid tumor

NCT03313778

BioNTech/Pfizer BNT162b2

LNP

COVID-19

/

Moderna mRNA-1273

LNP

COVID-19

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Crucell Berna Biotech Epaxal

Liposome (DOPE, DOPC)

Hepatitis A

/

Crucell Berna Biotech Inflexal V

Liposome (DOPE, DOPC)

Influenza

/

Creative Biolabs| Lipid-based mRNA Vaccine

Vaccine Formulation Development Service

mRNA Construction

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5’ Cap: The efficiency of capping and the cap structure impact innate sensing and protein production.

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UTR’s: Translational efficiency is regulated by their length, structures and regulatory elements.

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CDS: Modification of sequence, such as codon optimization, have contributed to improved expression.

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3’ Poly A-tail: Properties such as length, are important for translation and protection of the mRNA molecule.

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Purity: Removal of impurities reduces innate sensing promoting expression.

Creative Biolabs| Lipid-based mRNA Vaccine

Vaccine Formulation Development Service As a modularized nano carrier, the composition of liposomes can be customized according to requirements.

Category and proportion of lipids are adjustable for different characteristics and functions. Since we have mastered a series of liposome preparation methods, Creative Biolabs can also provide the development service of specific lipids.

Cationic lipid nanoparticle Cationic lipid, Cholesterol nanoparticle

Cationic lipid, Cholesterol, PEG nanoparticle

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Ionizable cationic lipid

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PEG-lipid

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Helper lipid

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Buffer/Excipients

Creative Biolabs| Lipid-based mRNA Vaccine

Vaccine Analytics & Assessment Service Safety and effectiveness of the vaccine need to be evaluated before clinical studies. With years of experience in vaccines development field, Creative Biolabs provides a series of analytics and assessment services to ensure the safety and effectiveness of your vaccine product.

Our Vaccine Analytics & Assessment Service includes but not limited to: In Vitro Assays

Safety Test •

Safety Pharmacology

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Immunization-challenge test

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Local tolerance

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Cell-based assays

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Single dose toxicity test

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Titration assays

Identity Test

In Vivo Assays

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Detection of attenuation degree

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Mice

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The reliability of inactivation

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Rats

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The allergen detection •

Rabbits

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Guinea Pigs

Stability Test •

Forced degradation studies

Creative Biolabs| Lipid-based mRNA Vaccine

About US

Along with the worldwide explosion of Covid-19, researchers are devoted to development of mRNA vaccines. Creative Biolabs has successfully established both drug delivery platforms and preclinical vaccine platforms. With years of experiences in the field of human health improvement, we have absolute advantages in providing the first-class products and related services on lipidbased mRNA vaccines development.

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Professional pre-clinical vaccine platforms

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Advanced equipment to produce various lipid-based drug delivery formulations

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First-in-class technology and expertise for characterization and validation of formulations

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Pharmaceutical scientists for scientific research

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Abundant experience in various applications

Creative Biolabs| Lipid-based mRNA Vaccine

Contact SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA Tel: 1-631-871-5806 Fax: 1-631-207-8356 Email: info@creative-biolabs.com Web: www.creative-biolabs.com/lipid-based-delivery/

Creative Biolabs| Lipid-based mRNA Vaccine