mRNA Vaccine A brief introduction of a novel vaccine technology
Address: 45-1 Ramsey Road, Shirley, NY 11967, USA Email: info@creative-biolabs.com Web: www.creative-biolabs.com
Contents 1
mRNA and mRNA vaccine
2
Characteristics of mRNA vaccine
3
Mechanism of action of mRNA-based vaccines
4
Types of mRNA vaccine
5
Delivery strategies of mRNA vaccine
6
Administration routes for mRNA vaccines
7
Creative Biolabs’ mRNA vaccine platforms
What is mRNA and mRNA vaccine? Messenger RNA （ mRNA ）
•
Responsible for transferring genetic information from DNA to protein
•
A template for protein translation
mRNA Vaccine
•
A novel vaccine technology which delivers the mRNA that encoding the antigen protein of pathogen to the cell, expresses the antigen protein, and then stimulates the immune response of the body.
Characteristics of mRNA Vaccine Comparison among characteristics of different vaccine types Types
Immunogenicity
Safety
Antibody specificity
Composition
manufactur R&D e cycle
immune response
Application
Attenuated/ inactivated vaccine
Strong
Low
low
Not clear
simple
8 years+
Cellular immunity; Humoral immunity
Prophylactic vaccine
Subunit vaccine
weak
High
high
clear
Complicate d
8 years+
Cellular immunity or Humoral immunity
Therapeutic vaccine; Prophylactic vaccine
DNA vaccine
weak
Controversial
low
clear
simple
3~5 years
mRNA vaccine
Strong
High
high
clear
simple
3~5 years
Cellular immunity; Humoral immunity
Therapeutic vaccine; Prophylactic vaccine
Mechanism of Action of mRNA-Based Vaccine 1
mRNA encapsulated in the delivery vehicle is taken up by APC cell.
2
Delivery vehicle is digested, and mRNA released.
3
mRNA is translated by the host’s ribosome and antigen is formed.
4
After the antigen is formed, it can be processed through different pathways.
(Opportunities and Challenges in the Delivery of mRNA-based vaccine)
Types of mRNA vaccine Non-replicating mRNA Self-amplifying mRNA
Open reading frame is a nucleic acid sequence that encodes antigens.
Open Reading Frame
5’-G
P P P UTR
CAP Cap enables mRNA to translate in the right direction.
SP
5‘Untranslated Region
ORF
UTR
3‘Untranslated Region
Regulatory elements in 5'U T R and 3'U T R stabilize mRNA and increase antigen protein translation.
AAAAAA(140-150)-3’ Poly A Tail Poly A can increase the mRNA stability and the expression of antigen protein, playing an important role in the translation and stability of mRNA.
Types of mRNA vaccine Non-replicating mRNA
Non-structural genes for self-amplification.
Insert Fragment
Self-amplifying mRNA
5’-G
CAP
P P P UTR
nsP4
nsP3
nsP2 nsP1
Virus-derived self-amplifying mRNA is to insert the nucleic acid sequence encoding antigen directly into singlestranded RNA virus, such as Semliki forest virus, yellow fever virus, etc.
5‘Untranslated Region
SP
ORF
CAP
UTR
AAAAAA(140-150)-3’
3‘ Untranslated Region
Poly A Tail
Delivery Strategies of mRNA Vaccine Liposomes
Delivery Carriers of mRNA Vaccines
Adeno-associated virus
Lentivirus
Sendai virus
Dendritic cell
Viral Carriers
Non-viral Carriers
Inorganic nanoparticles
Cationic cell membranepenetrating peptides
Delivery Strategies of mRNA Vaccine Liposome delivery mRNA has unique advantages 1
Liposomes are spherical vesicles, which can encapsulate mRNA to resist the action of nuclease;
2
Liposomes are similar to cell membrane and are easy to fuse with recipient cells, and the transfection efficiency is high;
3
Liposomes can deliver different sizes of mRNA;
4
Liposomes as delivery carriers are not restricted by the host. Up until now, lipid vectors have become the most effective non-viral vectors for delivering mRNA.
Delivery Strategies of mRNA Vaccine Naked mRNA Vaccines mRNA vaccines can be delivered without any additional carriers, that is, in a naked format. In this method, mRNA is dissolved in buffer and then injected directly. Advantages: 1. Easy to store and prepare. In the presence of storage reagents such as 10% trehalose, freeze-dried naked RNA can remain stable for up to 10 months at 4℃. 2. Vaccines made from unmodified nucleotides have dual advantages in innate immunogenicity. Immunogenicity may be beneficial to vaccination by providing some adjuvant activity. On the other hand, the activation of some RNA sensors may inhibit mRNA translation in the cytoplasm.
Delivery Strategies of mRNA Vaccine DC-Based mRNA Vaccines Autologous DC from primary human PBMCs is the main source for the preparation of mRNA-treated DC for in vivo applications. The main strategies for the transmission of mRNA to DC are electroporation and lipid-derived carriers.
Advantages: 1. Effective APC is essential for innate / adaptive immunity. 2. Biocompatibility
Administration Routes for mRNA Vaccines Main injection routes include intradermal (ID) injection, subcutaneous (SC) injection, intramuscular (IM) injection, nodule (IN) injection and intravenous (IV) injection.
Intradermal Injection
Deliver mRNA vaccine directly into the dermis and make it extracted by APC cells.
The disadvantage is that it has local side effects, and the injection volume is limited.
Subcutaneous Injection
Have a larger injection volume and reduce local adverse reactions. The absorption rate of SC region is very slow, which may lead to accidental degradation of mRNA vaccine.
Intravenous Injection
Intramuscular Injection
Send mRNA vaccine directly into APC and lymphoid organs.
Recruit different types of immune cells and recycle them to the injection site.
mRNA can be easily degraded through this routes.
The local reaction of intramuscular injection is mild, but the injection volume is limited.
Intranodal Injection APC in the lymphoid organs can easily phagocytize the injected mRNA vaccine, which improves the efficacy of the vaccine. The vaccination procedure is complicated.
(Formulation and Delivery Technologies for mRNA Vaccines)
Creative Biolabs’ mRNA Vaccine Platform Non-replicating mRNA Vaccine Platform
mRNA Vaccine Platform
Non-replicating mRNA vaccines
Dendritic Cell mRNA Vaccines Personalized Neoepitope mRNA Cancer Vaccines
mRNA Pharmacology Optimization Platform Optimization Service of mRNA Translation and Stability Services of Immunogenicity Modulation Effective mRNA Delivery Service
CREATIVE BIOLABS
mRNA GMP Synthesis
Self-amplifying mRNA (SAM) Vaccine Platform SAM vaccine design Synthesis of SAM vaccine Optimization of SAM vaccines Preclinical evaluation of SAM vaccine
mRNA Vaccine
Address: 45-1 Ramsey Road, Shirley, NY 11967, USA Email: info@creative-biolabs.com Web: www.creative-biolabs.com
