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mRNA VACCINES.pptx
The document is a seminar presentation on mRNA vaccines, highlighting their mechanism, history, delivery methods, applications, advantages, and disadvantages. It details the role of lipid nanoparticles in the delivery of mRNA vaccines and discusses their potential in rapid vaccine development for pandemics like COVID-19. The seminar concludes with the recognition of mRNA vaccines as a groundbreaking advancement in vaccinology, with ongoing research indicating their future potential in treating other diseases.
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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
- 2. CONTENTS 1.Introduction 1.1mRNA Vaccines 1.2 mRNA 2.Mechanism 2.1Antigen Antibody Interaction 3.History 4.Delivery 4.1 Lipid Nanoparticles 5.Types 6.Case Study 7.Applications 8.Advantages 9.Disadvantages 10.Conclusion 11.References
- 3.
- 4. 1.1 mRNA Fig.2 mRNATranscription CARRIES GENETIC INFORMATION FROM DNA TEMPLATE FOR PROTEIN SYNTHESIS SINGLE-STRANDED READ IN 5' TO 3'
- 5. 2. MECHANISM Fig2. Mechanismof 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 ANTIBODYINTERACTION 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 DLane, 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
- 8. Fig6. Illustration ofmRNA with it’s component parts
- 9. 4. DELIVERY Fig5. Variousmethods 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 ASOF 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
- 12. Fig6.Graph showing dailynew cases comparing v/s total doses administered
- 13. 7. APPLICATIONS SELF AMPLIFYINGMRNA 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 • Noactual 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.
- 15. mRNA Vaccines CurrentlyUnder Development
- 16. 8. ADVANTAGES • NOACTIVE 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 • mRNAis 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 Thepotential 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 DLane, 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.
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Editor's Notes
- #4 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.
- #5 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.
- #7 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.
- #11 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.
- #12 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.
- #17 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.
- #18 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.