This slide tries to explain and introduce you to the mRNA Vaccine Technology, describes mRNA Vaccines, Mechanism , Delivery, some research and case study of pandemic and advantages disadvantages & application see for yourself in detail.
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mRNA VACCINES.pptx
1. SEMINAR ON
“mRNA VACCINES”
By:- AMIT BARAIKAR
Under the Guidance of:- Prof. YOGESH MOHARKAR
DEPARTMENT OF BIOTECHNOLOGY
PRIYADARSHINI COLLEGE OF ENGINEERING, NAGPUR
2022-2023
4. 1.1 mRNA
Fig.2 mRNA Transcription
CARRIES GENETIC INFORMATION FROM DNA
TEMPLATE FOR PROTEIN SYNTHESIS
SINGLE-STRANDED READ IN 5' TO 3'
5. 2. MECHANISM
Fig2. Mechanism of action of mRNA Vaccine
mRNA vaccines work by introducing a piece of mRNA that corresponds to a viral protein,
usually a small piece of a protein found on the virus’s outer membrane
by encoding production of that part in an mRNA
(Individuals who get an mRNA vaccine are not exposed to the virus
nor can they become infected by the vaccine.)
6. 2.1 ANTIGEN ANTIBODY INTERACTION
Fig3,4. Antigen Antibody Interaction
ANY FOREING SUBSTANCE THAT ENTER
BODY & CAN CAUSE DISEASE IS ANTIGEN
ANTIBODIES ARE PRODUCED BY B CELLS OF
WBC CELLS
ANTIGEN & ANTIBODY COMBINE BY THE
PROCESS CALLED AGGLUTINATION
IN THE BLOOD ANTIGEN ARE BOUND BY
ANTIBODIES TO FORM ANTIGEN ANTIBODY
COMPLEX
• THIS COMPLEX IS LATER IS TRANSPORTED
• WHERE IT CAN BE DESTROYED OR
• DEACTIVATED AND WE REMAIN SAFE FROM
• ANTIGENS
7. 3. HISTORY
1971
C D Lane, G
Marbaix, J B
Gurdon.
Rabbit haemoglobin
synthesis in frog
cells.
1989
Malone
RW, Felgner
PL, Verma IM.
First use of mRNA
as an Vaccine .
2005
Kariko,Buckstein
M, Ni H, Weissman
D.
Mammalian RNA is
modified until
needed for the
creation of protein
9. 4. DELIVERY
Fig5. Various methods to deliver mRNA vaccine
LIPID
BASED
DELIVERY
POLYMER
BASED
DELIVERY
PEPTIDE
BASED
DELIVERY
VIRUS LIKE
REPLICATION
PARTICLE
CATIONC
NANO-
EMULSION
NAKED
MRNA’S
WHY LIPID BASED DELIVERY IS BEST ?
• NO BIOTOXICITY
• AVOIDS ORGANIC SOLVENTS
• LIPPOPHOLIC AND HYDROPHILLIC DRUG
INCORPORATION
• MODIFIED RELEASE PATTERNS.
• INCREASED DRUG STABILITY
• FEASIBLE TO SCALE UP AND STERLISATION
• LIMITED DRUG LOADING CAPACITY
• BIODEGRADIBLITY
• BIOCOMPATIBLITY
10. 4.1 LIPID NANOPARTICLES (LNP’S)
Fig6,7. lipid nanoparticles
• COMPOSED OF LIPIDS
• PHARMACEUTICAL DRUG DELIVERY
SYSTEM
• FIRST APPROVED IN 2018 FOR THE siRNA
DRUG ONPATTRO
• IN COVID-19 VACCINES COAT THE
FRAGILE mRNA STRANDS
WITH PEGYLATED LIPID NANOPARTICLES AS
THEIR DELIVERY VEHICLE
(MODERNA AND PFIZER–BIONTECH COVID-
19 VACCINES)
• HAVING SIZE ABOUT 10 TO 1000
NANOMETERS
• SPHERICAL IN SHAPE AND CONSISTS OF A
SOLID LIPID CORE
11. 6. CASE STUDY
AS OF 4 NOVEMBER 2022, THERE HAVE BEEN 628,694,934 CONFIRMED CASES
INCLUDING 6,576,088 DEATHS
1 NOVEMBER 2022, A TOTAL OF 12,861,382,558 VACCINE DOSES HAVE BEEN ADMINISTERED.
COVID 19
13. 7. APPLICATIONS
SELF AMPLIFYING MRNA VACCINES
• Utilize virus genetic replication machinery to
amplify the mRNA message within the cell.
• That lower dosing is required to produce the
same expression level.
PANDEMIC RESPONSE
• Rapid vaccine development and
manufacturing is critical.
• Once sequence is known mRNA vaccine
candidates can quickly be designed and tested.
• mRNA Vaccines function consistently
regardless of sequence.
• rapid scale-up of manufacturing.
14. mRNA VACCINES
• No actual pathogen utilized in a live attenuated,
inactivated, or subunit format.
• Rapid development timelines and lower risk.
• Enabling the immune system to mount a
response and form memory.
PERSONALIZED CANCER VACCINES
• Easily tailored to express a specific target
protein or epitope.
• mRNA is used to express tumor-associated
epitopes in host cells.
• Once presented by the cell, the patient’s own
immune system will recognize the antigen and
mount a response against the cancer.
16. 8. ADVANTAGES
• NO ACTIVE PATHOGEN INVOLVED
• STIMULATE CELLULAR IMMUNITY, AS
WELL AS HUMORAL IMMUNITY
• MANUFACTURED FASTER
• RESPONSIVENESS TO PANDEMICS
• MODIFIED NUCLEOSITES
SUPPRESS IMMUNE RESPONSE
STIMULATION
• NO RISK OF LOCALISED OUTBREAKS
• DESIGNED SWIFTLY
• CHEAP
• STANDARDIZED (FEWER ERROR RATES)
• DOESN’T ENTER CELL NUCLEUS SO
INTEGRATION WITH HOST GENOME IS
AVERTED.
17. 9. DISADVANTAGES
1.STORAGE
• mRNA is fragile
• must be kept at very low
temperatures to avoid
degrading
• Pfizer BioNTech
BNT162b2 mRNA vaccine
has to be kept between −80
and −60 °C
• Moderna says their mRNA-
1273 vaccine can be stored
between −25 and −15 °C
2.RECENT
• Before 2020 no mRNA
technology platform (drug
or vaccine) had been
authorized for use
• There was risk of unknown
effects
• Emergency use
authorisation was required
3.SIDE EFFECTS
• Reactogenicity
• unintended immune
reaction
18. 10. CONCLUSION
The potential advantages of mRNA as a vaccine range from the discovery of immunogens
to rapid response manufacturing. Currently, the field is pursuing two approaches: non-
replicating and self-replicating constructs.
Progress in mRNA technologies and lipid nanoparticle based delivery systems has allowed
the development of mRNA COVID-19 vaccines at unprecedented speed, demonstrating
the clinical potential of lipid nanoparticle–mRNA formulations and providing a powerful
tool against the pandemic.
The mRNA vaccines were never considered a sure thing we had to do the research,
testing which is why it took until 2020 but there was existing research which let us to
create these vaccines even faster. It was explosive development an incredibly swift global
collaboration in the name of human health something that feels to me on scale of apollo
mission .
Multiple mRNA vaccines are going under clinical trials for viral and bacterial diseases and
even for some cancers , mRNA vaccines are working its likely they will keep working and
that is great news for all of us.
19. 11. REFERENCES
1.C D Lane, G Marbaix, J B Gurdon et al. Rabbit haemoglobin synthesis in frog cells: the
translation of reticulocyte 9 s RNA in frog oocytes, ELSEVIER,1971,
https://doi.org/10.1016/0022-2836(71)90207-5.
2. Malone RW, Felgner PL, Verma IM (August 1989). "Cationic liposome-mediated RNA
transfection". Proceedings of the National Academy of Sciences of the United States of
America. 86 (16): 6077–81. Bibcode:1989PNAS...86.6077M.
3.Kariko K, Buckstein M, Ni H, Weissman D (August 2005). "Suppression of RNA
recognition by Toll-like receptors: the impact of nucleoside modification and the
evolutionary origin of RNA“. Immunity. 23 (2): 165–
75. doi:10.1016/j.immuni.2005.06.008. PMID 16111635.
4.Lu Lu, Jiarui Li, Mohammed Moussaoui and Ester Boix . " immune Modulation by
Human Secreted RNases at the extracellular Space " , Frontiers in immunology,
Doi: 10.3389/fimmu.2018.01012 .
5.Xucheng Hou, Tal Zaks, Robert Langer & Yizhou Dong, " Lipid nanoparticles for mRNA
delivery " Nat Rev Mater 6, 1078–1094 (2021). https://doi.org/10.1038/s41578-021-
00358-0.
20. 6.Oliver J Watson, Gregory Barnsley, Jaspreet Toor, Alexandra B Hogan,Peter Winskill, Prof
Azra C Ghani, " Global impact of the first year of COVID-19 vaccination: a mathematical
modelling study " DOI: https://doi.org/10.1016/S1473-3099(22)00320-6.
7.Cuiling Zhang1, Giulietta Maruggi 2, Hu Shan1 and Junee Li 1 , Advances in mRNA
Vaccines for Infectious Diseases, frontiers in immunology ",
Doi: 10.3389/fimmu.2019.00594
8.Anna Graczyk, Roza Pawlowska, Dominika Jedrzejczyk and Arkadiusz Chworos, Gold
Nanoparticles in Conjunction with Nucleic Acids as a Modern Molecular System for
Cellular Delivery,MDPI, doi:10.3390/molecules25010204
9.Norbert Pardi1, Michael J. Hogan1, Frederick W. Porter2 and Drew Weissman1 , mRNA
vaccines — a new era in vaccinology , Department of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania 19104, USA. doi:10.1038/nrd.2017.243
10.Nicholas A. C. Jackson, Kent E. Kester , Danilo Casemiro, Sanjay Guru Nathan and Frank
DeRosa, The promise of mRNA vaccines: a biotech and industrial perspective, npj Vaccines
(2020) 5:11 ; https://doi.org/10.1038/s41541-020-0159-8.
11.Hou, X., Zaks, T., Langer, R. et al. " Lipid nanoparticles for mRNA delivery ". Nat Rev
Mater 6, 1078–1094 (2021). https://doi.org/10.1038/s41578-021-00358-0.
An mRNA vaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into cells, which use the designed mRNA as a blueprint to build foreign protein that would normally be produced by a pathogen(such as a virus).
These protein molecules stimulate an immune response that teaches the body to identify and destroy the corresponding pathogen. The mRNA is delivered by encapsulated in lipid nanoparticles that protect the RNA strands and help their absorption into the cells.
In molecular biology messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene , and is read by a ribosome in the process of synthesizing a protein.
Antigen-antibody interaction, or antigen-antibody reaction, is a specific chemical interaction between antibodies produced by B cells of the white blood cells and antigens during immune reaction.
The antigens and antibodies combine by a process called agglutination. It is the fundamental reaction in the body by which the body is protected from complex foreign molecules, such as pathogens and their chemical toxins.
In the blood, the antigens are specifically and with high affinity bound by antibodies to form an antigen-antibody complex. The immune complex is then transported to cellular systems where it can be destroyed or deactivated.
mRNA requires safe, effective and stable delivery systems that protect the nucleic acid from degradation and that allow cellular uptake and mRNA release.
lipid nanoparticles are novel drug delivery systems which have many advantages over other Nano carriers. The most important advantages of lipid carriers are their biocompatibility, biodegradability, ease of scalability, and controlled and modified release patterns.
COVID 19
When the covid 19 pandemic began the researchers said the earliest possible window for vaccine would be end of 2020 and one pharma company pfizer/ biontech began rolling out in some parts of the world. .
Globally 4 November 2022, there have been 628,694,934 confirmed cases of COVID-19, including 6,576,088 deaths, reported to WHO. As of 1 November 2022, a total of 12,861,382,558 vaccine doses have been administered.
WHO has evaluated that the following vaccines against COVID-19 have met the necessary criteria for safety and efficacy: AstraZeneca/Oxford vaccine, Johnson and Johnson , Moderna, Pfizer/BionTech ,Sinopharm ,Sinovac , COVAXIN,Covovax,Nuvaxovid,CanSino.
Total 21 vaccines now being rolled out in countries worldwide.
mRNA vaccines are not constructed from an active pathogen (or even an inactivated pathogen), they are non-infectious . In contrast, traditional vaccines require the production of pathogens, which, if done at high volumes, could increase the risks of localized outbreaks of the virus at the production facility
Biological advantage of mRNA vaccines is that since the antigens are produced inside the cell, they stimulate cellular immunity, as well as humoral immunity.
mRNA vaccines have the production advantage that they can be designed swiftly just by using genetic information.Moderna designed their mRNA-1273 vaccine for COVID-19 in 2 days.They can also be manufactured faster, more cheaply, and in a more standardized fashion (with fewer error rates in production), which can improve responsiveness to serious outbreaks.
The mRNA is translated in the cytosol, so there is no need for the RNA to enter the cell nucleus, and the risk of being integrated into the host genome is averted.
Modified nucleosides can be incorporated to mRNA to suppress immune response stimulation to avoid immediate degradation and produce a more persistent effect through enhanced translation capacity.
Storage: Because mRNA is fragile, some vaccines must be kept at very low temperatures to avoid degrading and thus giving little effective immunity to the recipient. Pfizer BioNTech's BNT162b2 mRNA vaccine has to be kept between −80 and −60 °C (−112 and −76 °F).Moderna says their mRNA-1273 vaccine can be stored between −25 and −15 °C (−13 and 5 °F),which is comparable to a home freezer, and that it remains stable between 2 and 8 °C (36 and 46 °F) for up to 30 days.
Recent: Before 2020, no mRNA technology platform (drug or vaccine) had been authorized for use in humans, so there was a risk of unknown effects. The 2020 COVID-19 pandemic required faster production capability of mRNA vaccines, made them attractive to national health organizations & led to debate about the type of initial authorization mRNA vaccines should get emergency use authorization after the eight-week period of post-final human trials.
Side effects: Reactogenicity is similar to that of conventional, non-RNA vaccines. However, those susceptible to an autoimmune response may have an adverse reaction to mRNA vaccines. The mRNA strands in the vaccine may elicit an unintended immune reaction – this entails the body believing itself to be sick, and the person feeling as if they are as a result. To minimize this, mRNA sequences in mRNA vaccines are designed to mimic those produced by host cells.