VIETNAM GENERAL CONFEDERATION OF LABOUR TON DUC THANG UNIVERSITY FACULTY OF APPLIED SCIENCE MICROBIOLOGY REPORT RECOMBINANT VACCINE Instructing lecturer: Trần Thị Tuyết Nhung Group: Tăng Quốc Kỳ – 620H0271 Lương Thị Quỳnh Mai – 620H0273 Âu Dương Vịnh Huy – 620H0051 Ho Chi Minh City, 2021 i ACKNOWLEGDEMENT First, I would like to thank Ton Duc Thang University for giving me the opportunity to access learning microbiology In particular, I would like to express my deep thanks to my lecturer – Tran Thi Tuyet Nhung for imparting valuable, influential and highly applicable lessons From what you conveyed, I gradually expand my knowledge, comprehend the small world that the naked eye could not see, understand the cycle of microorganisms and bacteria Perhaps knowledge is endless and each person's acquisition has certain limitations For over the year, our country has also been heavily affected by the Covid-19 pandemic leading to our knowledge disruption Therefore, in the process of completing the report, it is inevitable to avoid the shortcomings or mistakes I look forward to receiving comments from you to gain more experience for later reports and essays I would like to sincerely thank and wish you and other teachers have excellent health to overcome this pandemic together ii TABLE OF CONTENTS ACKNOWLEGDEMENT TABLE OF CONTENTS LIST OF ABBREVIATIONS LIST OF TABLES LIST OF PICTURES INTRODUCTION CHAPTER 1: DEFINITION AND DIFFERENCE OF VACCINES 1.1Traditional vaccine definition 1.2Definition of recombinant vaccine: 1.3The difference between traditional vaccine and r CHAPTER 2: CORONAVIRUS DISEASE 2019 (COVID-19) 2.1Introduction 2.2Structure 2.3Simplified mechanism of Covid action CHAPTER 3: POPULAR RECOMBINANT COVID-19 VACCINES 3.1Vector vaccine 3.1.1Overview 3.1.2Mechanism o 3.1.3Safety and eff 3.2mRNA vaccine 3.2.1Overview 3.2.2Mechanism o 3.2.3Safety and eff 3.3Protein subunit vaccine iii 3.3.1 Overview 15 3.3.2 Mechanism of action 16 3.3.3 Safety and efficiency 18 REFERENCES 19 RESPONSIBILITY 24 iv LIST OF ABBREVIATIONS ACE2 Angiotensin-converting enzyme COVID Coronavirus disease DNA DeoxyriboNucleic Acid ER Endoplasmic Reticulum mRNA Messenger RNA RNA RiboNucleic acid TMPRSS2 Transmembrane serine protease iii LIST OF TABLES Table 1.1 Comparison between traditional vaccines and recombinant vaccines iv LIST OF PICTURES Chapter Picture 1.1 Various approaches for vaccine development Picture 1.2 The different components between traditional and recombinant vaccine Picture 1.3 The estimated product time of these vaccines Picture 1.4 Immunological mechanism of conventional and mRNA vaccine .4 Chapter Picture 2.1 Report cases and deaths by countries Picture 2.2 The structure of Coronavirus Picture 2.3 Mechanism action of Coronavirus Chapter Picture 3.1 An overview of Vector vaccine manufacturing Picture 3.2 A simplified illustration of how recombinant Vector vaccines triggeres immune reactions to protect our body 11 Picture 3.3 An overview recombinant mRNA vaccine manufacturing 12 Picture 3.4 An overvier illustration of how recombinant mRNA vaccine triggers immune system to protect our body 14 Picture 3.5 Simplified process of making recombinant protein vaccine 16 Picture 3.6 Overview of immune reactions triggered by recombinant protein vaccine and its role in protecting against COVID - 19 18 v INTRODUCTION Covid is a pandemic today, spreading and growing rapidly Over the past two years, it has left countless losses around the world, millions of deaths, more than hundreds of millions of infections and the rate of spread shows no signs of stopping That is why, the governments of countries require accelerated vaccinations to prevent the outbreak of pandemics and the emergence of new variants Vaccination against SARS-CoV-2 will probably provide the most effective interventional long-term means of preventing and controlling SARS-CoV-2 infection, and it has become an urgent global priority Fortunately, my group has the topic, which almost everyone is interested in, "Recombinant Vaccine" with the scope of talking about "Covid 19" The purpose of our group through this report is introducing and giving people a deeper understanding of the vaccines that we are vaccinated with as well as understand the mechanism of vaccines This report consists of three chapters: Chapter 1: Definition and difference of vaccines Chapter 2: Coronavirus Disease 2019 (COVID-19) Chapter 3: Types of popular Recombinant Covid-19 vaccines CHAPTER 1: DEFINITION AND DIFFERENCE OF VACCINES 1.1 Traditional vaccine definition Vaccine is a biological preparation that provides active acquired immunity against a certain disease Usually, a vaccine consists of a biological agent that represents the disease-causing microorganism It is often made from a weakened or killed form of the microorganism, its toxins or one of its surface protein antigens The first successful case of vaccination was performed by Edward Jenner in 1796 [1] 1.2 Definition of recombinant vaccine: Recombinant vaccine is a vaccine produced through recombinant DNA technology This involves inserting the DNA encoding an antigen (such as a bacterial surface protein) that stimulates an immune response into bacterial or mammalian cells, expressing the antigen in these cells and then purifying it from them [2] Picture 1.1 Various approaches for vaccine development Vaccine generated using recombinant DNA technology is called recombinant vaccine Recombinant vaccines can be created in many different methods These types of vaccines are manufactured with the assistance of expression systems, such as bacteria, insect, yeast, plant, mammalian, and cell-free [1] While there are various types of vaccines made possible by recombinant DNA technology, recombinant vaccines can be classified into two major categories: Genetic approaches vaccines and Recombinant (protein subunit) vaccines [1] 1.3 The difference between traditional vaccine and recombinant vaccine The definition: Traditional vaccines contain a dead or disabled virus, designed to be incapable of causing severe disease while also provoking an immune response against the live virus [3] While recombinant vaccines are products of genetic engineering, where a harmless agent, is programmed to produce antigens of harmful pathogens [4] The components: The traditional one contains weakened microbial protein or inactive microbe but the recombinant vaccine is more types such as: mRNA, bacterial vector, subunit,… Picture 1.2 The different components between traditional and recombinant vaccine 11 Picture 3.2 A simplified illustration of how recombinant Vector vaccines trigger immune reactions to protect our body 3.1.3 Safety and efficiency Almost viral vector-based vaccines are about 60% - 80% effective in preventing COVID-19 The 2nd dose is needed to further reduce the virus’s ability to spread and to strengthen and prolong immunity [13] People in the COVID-19 vaccine trials for this vaccine commonly had soreness where the shot was given, tiredness, headaches, muscle aches, and nausea for a day or two [14] Fewer people had redness and swelling at the injection site [14] Other problems may arise by chance and are 12 unrelated to vaccination, such as a cold or gastroenteritis Most reactions are quite mild and short-lived [13] The vaccines cannot cause COVID-19 because they not contain the SARS-CoV-2 virus responsible for the disease [13] 3.2 mRNA vaccine 3.2.1 Overview Picture 3.3 An overview recombinant mRNA vaccine manufacturing mRNA vaccines are a new type of vaccine to protect against infectious diseases mRNA vaccines teach our cells how to make a protein - or even just a piece of a protein - that triggers an immune response inside our bodies [15] That immune response, which produces antibodies, is what protects us from getting infected if the real virus enters our bodies [15] The mRNA does not enter the nucleus and therefore cannot be incorporated into the genome [16] Its presence in the cell is transient, and it is quickly metabolized and eliminated via cellular processing mechanisms [16] The Pfizer-BioNTech vaccine, BNT162b2, uses mRNA to create the receptor binding domain of the spike protein of SARS-CoV-2 The spike protein is what SARS-CoV-2 uses to attach to host cells and enter them The Moderna vaccine, mRNA-1273, uses mRNA to create the SARS-CoV-2 spike protein stabilized in its prefusion conformation [16] 13 3.2.2 Mechanism of action COVID-19 mRNA vaccines give instructions for our cells to make a harmless piece of what is called the “spike protein.” The spike protein is found on the surface of the virus that causes COVID-19 [15] First, COVID-19 mRNA vaccines are given in the upper arm muscle Once the instructions (mRNA) are inside the muscle cells, the cells use them to make the protein piece After the protein piece is made, the cell breaks down the instructions and gets rid of them [15] Next, the cell displays the protein piece on its surface Our immune systems recognize that the protein doesn’t belong there and begin building an immune response and making antibodies, like what happens in natural infection against COVID-19 [15] At the end of the process, our bodies have learned how to protect against future infection [15] 14 Picture 3.4 An overview illustration of how recombinant mRNA vaccine triggers immune system to protect our body 15 3.2.3 Safety and efficiency As of publication of this review, there have been no serious side effects identified in the ongoing phase clinical trials for both the Moderna and Pfizer/BioNTech mRNA vaccines [17] Mild local side effects including heat, pain, redness, and swelling are more common with the vaccines with most occurring within to days following vaccination [17] The benefit of mRNA vaccines, like all vaccines, is those vaccinated gain this protection without ever having to risk the serious consequences of getting sick with COVID-19 [15] As reported, a two-dose regimen of the mRNA vaccines resulted in 90 - 95 % protection against COVID-19 in people ages 16 and older, and over a median of months, safety of the vaccine was comparable to that of other viral vaccines [17] 3.3 Protein subunit vaccine 3.3.1 Overview Recombinant protein vaccines, also called recombinant subunit vaccines, is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response [18][19] A "subunit" vaccine doesn't contain the whole pathogen, unlike live attenuated or inactivated vaccine, but contains only the antigenic parts such as proteins, polysaccharides or peptides [18][19] The company that made the recombinant protein vaccine against Covid-19 is Novavax Besides Novavax, Nano Covax is also a vaccine using protein subunits Since the antigens alone in a subunit vaccine are insufficient to produce high immunogenicity, non-immunogenic materials known as adjuvants are typically incorporated into the vaccine formulation to improve the immune response and enhance the efficacy of the vaccine [20] For example, Novavax uses a proprietary adjuvant called Matrix-M, which is based on a type of compound found in many 16 plants called saponin [21] The company says it boosts the body's immune response and generates a bigger immune response with a lower dose [21] Picture 3.5 Simplified process of making recombinant protein vaccine 3.3.2 Mechanism of action Subunit vaccines for both SARS coronaviruses rely on eliciting an immune response against the S-spike protein to prevent its docking with the host ACE2 receptor [22] The vaccine is injected into the muscles of the arm Each injection includes many spike nanoparticles, along with a compound extracted from the soapbark tree The 17 compound attracts immune cells to the site of the injection and causes them to respond more strongly to the nanoparticles [23] Immune cells called antigen-presenting cells encounter the vaccine nanoparticles An antigen-presenting cell tears apart the spike proteins and displays some of their fragments on its surface A so-called helper T cell may detect the fragments If a fragment fits into one of its surface proteins, the T cell becomes activated Now it can recruit other immune cells to respond to the vaccine [23] B cell may also encounter the vaccine nanoparticles B cells have surface proteins in a huge variety of shapes, and a few might have the right shape to latch onto a spike protein If a B cell latch on, it can pull the vaccine particle inside and present spike protein fragments on its surface If a helper T cell activated against the spike protein latching onto one of these fragments, it activates the B cell Now the B cell proliferates and pours out antibodies that have the same shape as its surface proteins [23] 18 Picture 3.6 Overview of immune reactions triggered by recombinant protein vaccine and its role in protecting against COVID - 19 3.3.3 Safety and efficiency Because protein-based vaccine doesn't contain live components of the pathogen, there is no risk of introducing the disease, and is safer and more stable than vaccine containing whole pathogens However, this also means they’re less likely to produce longlasting immunity, which is why they often include the addition of an adjuvant – a substance used to boost the immune response Novavax recently released its Phase clinical trial results showing their vaccine was about 90% effective overall, which puts it on par with the vaccines produced by Pfizer-BioNTech and Moderna [24] 19 REFERENCES English Internet: [1] Recombinant vaccine, (Accessed: 01:31 PM, 14/10/2021) From: https://www.genscript.com/recombinant-vaccine.html [2] Recombinant vaccine, (Accessed: 05:51 PM, 14/10/2021) From: https://www.nature.com/subjects/recombinant-vaccine [3] Editors' Pick & JV Chamary (Nov 29, 2020), What’s The Difference Between Covid-19 Coronavirus Vaccines? (Accessed: 06 PM 14/10/2021) From: https://www.forbes.com/sites/jvchamary/2020/11/29/coronavirusvaccines-difference [4] Board Review in Preventive Medicine and Public Health, 2017, (Accessed: 06:02 PM 14/10/2021) From: https://www.sciencedirect.com/topics/medicine-and-dentistry/ recombinant-vaccine/ [5] Mulazim Hussain Bukhari, Mobin Syed & Shahzadi Zain, The Differences betwee al Vaccines and RNA Vaccines: Safety, Efficacy, Reliability and Future of COVID-19 Vaccines (2021), (Accessed: 06:11 PM 14/10/2021) From: https://annalskemu.org/journal/index.php/annals/article/view/4531 [6] Copyright © 2002-2020 Pfizer Inc, Advancing Medical Research: What Makes an RNA Vaccine Different from a Conventional Vaccine? (Accessed: 08:55 PM 14/10/2021) From: https://www.breakthroughs.com/advancing-medical-research/whatmakes-rna-vaccine-different-conventional-vaccine 20 [7] Anthony R Fehr and Stanley Perlman, M.D., Ph.D (2015), Coronaviruses: An Overview of Their Replication and Pathogenesis, (Accessed: 01:27 PM, 16/10/2021) From: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369385/ [8] Megan Scudellari, How the coronavirus infects cells — and why Delta is so dangerous (28 July 2021), (Accessed: 21:01 PM, 18/10/2021) From: https://www.nature.com/articles/d41586-021-02039-y/ [9] Neel V Patel, How does the coronavirus work? (April 15, 2020), (Accessed: 23:51 PM, 18/10/2021) From: https://www.technologyreview.com/2020/04/15/999476/explainer-howdoes-the-coronavirus-work/ [10] What are viral vector-based vaccines and how could they be used against COVID-19? (2021), (Accessed: 01:51 AM, 19/10/2021) From: https://www.gavi.org/vaccineswork/what-are-viral-vector-basedvaccines-and-how-could-they-be-used-against-covid-19 [11]What different types of Covid-19 vaccine are there? (8 December 2020), (Accessed: 02:26 AM, 19/10/2021) From: https://wellcome.org/news/what-different-types-covid-19-vaccine-arethere [12] National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases, Understanding Viral Vector COVID-19 Vaccines (Oct 18, 2021), (Accessed: 09:26 AM, 19/10/2021) From: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/differentvaccines/viralvector.html 21 [13] Viral Vector Vaccines (May 28, 2021), (Accessed: 09:32 AM, 19/10/2021) From: https://www.idsociety.org/covid-19-real-time-learning-network/ vaccines/covid-19-viral-vector-vaccines/#overview [14] COVID-19 viral vector-based vaccine, (Accessed: 10:27 AM, 19/10/2021) From: https://www.quebec.ca/en/health/advice-and-prevention/vaccination /covid-19-viral-vector-based-vaccine [15] Barry Zingman, MD & L Renee Watson, MSN, RN, Understanding the Viral Vector Covid-19 Vaccine (Oct 25, 2021), (Accessed: 10:33 AM, 19/10/2021) From: https://myhealth.ucsd.edu/Coronavirus/134,264 [16] National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases, Understanding mRNA COVID-19 Vaccines (Oct 18, 2021), (Accessed: 03:43 PM, 19/10/2021) From: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/differentvaccines/mrna.html [17] mRNA Vaccines (August 23, 2021), (Accessed: 06:43 PM, 19/10/2021)https://www.idsociety.org/covid-19-real-timelearning-network/vaccines/mrna-vaccines/ [18] Pratibha Anand & Vincent P Stahel, The safety of Covid-19 mRNA vaccines: a review (01 May 2021), (Accessed: 08:43 PM, 19/10/2021) From: https://pssjournal.biomedcentral.com/articles/10.1186/s13037-02100291-9 22 [19] What are protein subunit vaccines and how could they be used against COVID-19? (2021), (Accessed: 09:31 PM, 19/10/2021) From: https://www.gavi.org/vaccineswork/what-are-protein-subunit-vaccinesand-how-could-they-be-used-against-covid-19 [20] Module - Subunit vaccines (2020), (Accessed: 10:08 PM, 19/10/2021) From: https://vaccine-safety-training.org/subunit-vaccines.html [21] Benedette Cuffari, M.Sc., What is a Subunit Vaccine? (Mar 15, 2021), (Accessed: 10:15 PM, 19/10/2021) From: https://www.news-medical.net/health/What-is-a-Subunit-Vaccine.aspx [22] Files from CBC's Emily Chung, How the Novavax COVID-19 vaccine differs from those already approved in Canada (Feb 02, 2021), (Accessed: 10:27 PM, 19/10/2021) From: https://www.cbc.ca/news/health/novavax-explainer-1.5897946 [23] Jiang S, Bottazzi ME, Du L, Lustigman S, Tseng CT, Curti E, et al Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome Expert Rev Vaccines 2012;11(12):1405–13 (Accessed: 08:27 PM, 20/10/2021) From: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094941/ [24] Jonathan Corum & Carl Zimmer, How the Novavax vaccine works (May 7, 2021), (Accessed: 09:47 PM, 20/10/2021) From: https://www.nytimes.com/interactive/2020/health/novavax-covid-19vaccine.html 23 [25] Jackie Dunham CTVNews.ca Writer, COVID-19 vaccine explainer: How protein subunit shots work, what makes them different (July 21, 2021), (Accessed: 10:27 PM, 19/10/2021) From: https://www.ctvnews.ca/health/coronavirus/covid-19-vaccineexplainer-how-protein-subunit-shots-work-what-makes-them-different1.5493274 24 RESPONSIBILITY Content Format & Edit Productivity Attitude Shorten content for power point Edit 25 Productivity Attitude Translate into VietNamese Summary Productivity Attitude ... approaches for vaccine development Vaccine generated using recombinant DNA technology is called recombinant vaccine Recombinant vaccines can be created in many different methods These types of vaccines... types of vaccines made possible by recombinant DNA technology, recombinant vaccines can be classified into two major categories: Genetic approaches vaccines and Recombinant (protein subunit) vaccines... was performed by Edward Jenner in 1796 [1] 1.2 Definition of recombinant vaccine: Recombinant vaccine is a vaccine produced through recombinant DNA technology This involves inserting the DNA encoding