mRNA vaccines are a novel vaccine technology that deliver mRNA encoding the antigen protein of a pathogen. This allows the antigen protein to be expressed by the recipient's cells and stimulate an immune response. There are two main types of mRNA vaccines - non-replicating mRNA and self-amplifying mRNA. Delivery strategies include viral carriers like lentivirus or non-viral carriers like liposomes. Administration routes include intramuscular injection, intradermal injection, and intranodal injection. Creative Biolabs offers several mRNA vaccine platforms including non-replicating mRNA vaccines, self-amplifying mRNA vaccines, and dendritic cell mRNA vaccines.

1. A brief introduction of a novel vaccine technology
mRNA Vaccine
Address: 45-1 Ramsey Road, Shirley, NY 11967, USA
Email: info@creative-biolabs.com
Web: www.creative-biolabs.com

2. Contents
mRNA and mRNA vaccine
1
Characteristics of mRNA vaccine
2
Mechanism of action of mRNA-based vaccines
3
Types of mRNA vaccine
4
Delivery strategies of mRNA vaccine
5
Administration routes for mRNA vaccines
6
Creative Biolabs’ mRNA vaccine platforms
7

3. What is mRNA and mRNA vaccine?
Messenger RNA（mRNA）
• Responsible for transferring genetic
information from DNA to protein
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.
• A template for protein translation

4. Characteristics of mRNA Vaccine
Types Immuno-
genicity
Safety Antibody
specificity
Composition manufactur
e
R&D
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
Cellular
immunity;
Humoral
immunity
Therapeutic
vaccine;
Prophylactic
vaccine
mRNA
vaccine
Strong High high clear simple 3~5
years
Comparison among characteristics of different vaccine types

5. Mechanism of Action of mRNA-Based Vaccine
mRNA encapsulated in the delivery vehicle is
taken up by APC cell.
(Opportunities and Challenges in the Delivery of mRNA-based vaccine)
Delivery vehicle is digested, and mRNA released.
mRNA is translated by the host’s ribosome and
antigen is formed.
After the antigen is formed, it can be processed
through different pathways.
1
2
3
4

6. Types of mRNA vaccine
 Non-replicating mRNA
 Self-amplifying mRNA
Regulatory elements in 5'U T R and 3'U T R stabilize
mRNA and increase antigen protein translation.
5’-G
Cap enables mRNA to
translate in the right
direction.
Poly A can increase the mRNA
stability and the expression of antigen
protein, playing an important role in
the translation and stability of mRNA.
P P P UTR SP ORF UTR AAAAAA(140-150)-3’
CAP 5‘Untranslated Region 3‘Untranslated Region Poly A Tail
Open Reading Frame
Open reading frame is a nucleic acid
sequence that encodes antigens.

7.  Non-replicating mRNA
 Self-amplifying mRNA
Non-structural genes for
self-amplification.
Virus-derived self-amplifying mRNA is
to insert the nucleic acid sequence
encoding antigen directly into single-
stranded RNA virus, such as Semliki
forest virus, yellow fever virus, etc.
5’-G P P P UTR nsP4
ORF UTR AAAAAA(140-150)-3’
nsP3 nsP2 nsP1
SP
CAP 5‘Untranslated Region
Insert Fragment
CAP 3‘ Untranslated Region Poly A Tail
Types of mRNA vaccine

8. Delivery Strategies of mRNA Vaccine
Lentivirus
Adeno-associated
virus
Sendai virus
Delivery Carriers of mRNA Vaccines
Viral
Carriers
Non-viral
Carriers
Liposomes
Dendritic cell
Inorganic
nanoparticles
Cationic cell
membrane-
penetrating peptides

9. 1
2
3
4
Liposome delivery mRNA has unique advantages
Liposomes are spherical vesicles, which can encapsulate mRNA
to resist the action of nuclease;
Liposomes are similar to cell membrane and are easy to fuse
with recipient cells, and the transfection efficiency is high;
Liposomes can deliver different sizes of mRNA;
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

10. 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.
Naked mRNA Vaccines
Delivery Strategies of mRNA Vaccine

11. Delivery Strategies of mRNA Vaccine
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
DC-Based mRNA Vaccines

12. Administration Routes for mRNA Vaccines
(Formulation and Delivery Technologies for mRNA Vaccines)
 Deliver mRNA vaccine directly
into the dermis and make it
extracted by APC cells.
 Have a larger injection
volume and reduce local
adverse reactions.
Main injection routes include intradermal (ID) injection, subcutaneous (SC) injection, intramuscular (IM)
injection, nodule (IN) injection and intravenous (IV) injection.
 Send mRNA vaccine directly
into APC and lymphoid
organs.
 Recruit different types of
immune cells and recycle
them to the injection site.
 APC in the lymphoid organs can
easily phagocytize the injected
mRNA vaccine, which improves
the efficacy of the vaccine.
Intradermal Injection Subcutaneous Injection Intravenous Injection Intramuscular Injection Intranodal Injection
 The disadvantage is that it has
local side effects, and the
injection volume is limited.
 The absorption rate of SC
region is very slow, which
may lead to accidental
degradation of mRNA
vaccine.
 mRNA can be easily
degraded through this
routes.
 The local reaction of
intramuscular injection is
mild, but the injection
volume is limited.
 The vaccination
procedure is complicated.

13. Creative Biolabs’ mRNA Vaccine Platform
mRNA Vaccine Platform
 Dendritic Cell mRNA
Vaccines
 Personalized Neoepitope
mRNA Cancer Vaccines
 mRNA GMP Synthesis
Non-replicating mRNA Vaccine Platform
 Non-replicating mRNA
vaccines
mRNA Pharmacology Optimization Platform
 Optimization Service of
mRNA Translation and
Stability
 Services of Immunogenicity
Modulation
 Effective mRNA Delivery
Service
Self-amplifying mRNA
(SAM) Vaccine Platform
 SAM vaccine design
 Synthesis of SAM vaccine
 Optimization of SAM vaccines
 Preclinical evaluation of SAM
vaccine
CREATIVE
BIOLABS

14. mRNA Vaccine
Address: 45-1 Ramsey Road, Shirley, NY 11967, USA
Email: info@creative-biolabs.com
Web: www.creative-biolabs.com