Coronavirus (30) mRNA vaccine for COVID-19: an introduction
The UK's Medicines and Healthcare Products Regulatory Agency (MHRA) announced on 2nd November that they have granted authorisation for temporary supply of COVID-19 mRNA vaccine BNT162b2, from Pfizer and BioNTech, for active immunization of individuals aged 16 years old and over.1 This is the first vaccine receiving approval to be used for COVID-19 prevention in the UK. It is one of the mRNA vaccines which had entered Phase 3 according to the WHO's data.2 In this blog post, I am going to introduce you the mRNA vaccines.
What is an mRNA vaccine?
Conventional vaccines work by injecting either a dead form of the pathogen (for inactivated vaccines), or a weakened form of it (for live attenuated vaccines), into the body to trigger the production of antibodies against the pathogen. You may wonder how the pathogen can trigger the immune system. A portion of the pathogen called the antigen binds to B-cell surfaces and stimulates these B cells to divide and mature into a group of identical cells, called specific antibodies, that can recognize the antigen. Therefore the antigen, the portion of the new infectious agent—but not the whole infectious agent—initiates our immunity to recognize the pathogen and respond to it. Once the immunity against the pathogen is built, our immune system can respond quickly next time the same pathogen invades.
Based on this understanding of how human immunity against pathogens works, scientists recently developed the mRNA vaccine, which produces only an antigen that inititates specific antibody production and not the rest of the pathogen.3 According to Pfizer's website introducing mRNA vaccines, "mRNA vaccines work by introducing into the body a messenger RNA (mRNA) sequence that contains the genetic instructions for the vaccinated person’s own cells to produce the vaccine antigens and generate an immune response."4
The mRNA sequence for the mRNA vaccines are synthetic oligonucleotides*. Since mRNA is not very stable, the genetic materials include modified nucleosides to prevent degradation.5 Moreover, mRNA is highly vulnerable to degradation by enzymes, called extracellular RNases, in our body. Therefore, mRNAs of the mRNA vaccines are usually encapsulated within lipids or polymeric nanoparticles to protect the mRNAs and to enable entry of the mRNA into cells. These carrier systems are designed to protect mRNA from enzymes' degradation and also allow rapid uptake of the mRNA by human cells.3,6 Recent technology innovations, especially in nanotechnology, enables the synthesis of mRNA molecules with higher stability and the encapsulation of mRNA molecules in nanoparticles for efficient delivery of mRNA into target cells.5
Additionally, in order to provoke a stronger immune response, a booster shot is usually added after the first shot of the mRNA vaccine. The two mRNA vaccine candidates for COVID-19 that have entered phase 3 clinical trials both require 2 doses.
Advantages of mRNA vaccines over conventional vaccines
1. Faster and cheaper to produce: The process of producing mRNA is inexpensive, and could be standardised and scaled easily. This allows quick responses to large outbreaks and epidemics.3
2. Higher efficacy: There is no viral vector to carry mRNA, therefore the anti-vector immunity, which could decrease the efficacy of the vaccine, is avoided. Additionally, as there is no fear of anti-vector immunity, mRNA vaccines can be administered repeatedly.3
3. Safer: mRNA vaccine does not contain any viral component, neither inactivated disease-causing organisms or proteins made by pathogen. Thus there is no potential risk of infection or insertional mutagenesis. Moreover, mRNA is degraded by normal cellular processes, and its in vivo half-life can be regulated through the use of various modifications and delivery methods. The inherent immunogenicity of the mRNA can be down-modulated to further increase the safety profile.3
However, since mRNA vaccine is a new type of vaccine developed by new technology, it has never before been applied clinically. It is now too early to say the vaccine is totally safe. Long-term follow-up over many years on the people who have used mRNA vaccines is necessary to find out if there are any long-term side effects of this type of vaccine.
Both of the mRNA vaccine candidates for COVID-19 contain genetic codes for the Spike glycoprotein of SARS-CoV-2. My next two blog posts will take a closer look at the two mRNA vaccine candidates.
*Synthesized oligonucleotides are short fragments of nucleic acids with defined chemical structure manufactured by biotech companies. The technique of synthesizing oligonucleotides is very useful, as it provides a convenient and inexpensive way to produce custom-made fragments of nucleic acids with desired sequences.
References
1. Decision: Regulatory approval of Pfizer/ BioNTech vaccine for COVID-19. Gov.UK’s news release, 2nd Dec, 2020. https://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19
2. Draft landscape of COVID-19 candidate vaccines. World Health Orgainzation. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
3. N. Pardi, M.J. Hogan, F.W. Porter, et al. mRNA vaccines — a new era in vaccinology. Nat. Rev. Drug Discov. 2018 Apr; 17(4):261-279.
4. Behind the science: what is an mRNA vaccine? Pfizer's website. https://www.pfizer.co.uk/behind-science-what-mrna-vaccine
5. K. Kariko, H. Muramatsu, F.A. Welsh, et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther., 2008, 16(11), 1833–1840.
6. How nanotechnology helps mRNA Covid-19 vaccines work. By Elizabeth Cooney. STAT Biotech, 1st Dec., 2020. https://www.statnews.com/2020/12/01/how-nanotechnology-helps-mrna-covid19-vaccines-work/
The UK's Medicines and Healthcare Products Regulatory Agency (MHRA) announced on 2nd November that they have granted authorisation for temporary supply of COVID-19 mRNA vaccine BNT162b2, from Pfizer and BioNTech, for active immunization of individuals aged 16 years old and over.1 This is the first vaccine receiving approval to be used for COVID-19 prevention in the UK. It is one of the mRNA vaccines which had entered Phase 3 according to the WHO's data.2 In this blog post, I am going to introduce you the mRNA vaccines.
What is an mRNA vaccine?
Conventional vaccines work by injecting either a dead form of the pathogen (for inactivated vaccines), or a weakened form of it (for live attenuated vaccines), into the body to trigger the production of antibodies against the pathogen. You may wonder how the pathogen can trigger the immune system. A portion of the pathogen called the antigen binds to B-cell surfaces and stimulates these B cells to divide and mature into a group of identical cells, called specific antibodies, that can recognize the antigen. Therefore the antigen, the portion of the new infectious agent—but not the whole infectious agent—initiates our immunity to recognize the pathogen and respond to it. Once the immunity against the pathogen is built, our immune system can respond quickly next time the same pathogen invades.
Based on this understanding of how human immunity against pathogens works, scientists recently developed the mRNA vaccine, which produces only an antigen that inititates specific antibody production and not the rest of the pathogen.3 According to Pfizer's website introducing mRNA vaccines, "mRNA vaccines work by introducing into the body a messenger RNA (mRNA) sequence that contains the genetic instructions for the vaccinated person’s own cells to produce the vaccine antigens and generate an immune response."4
The mRNA sequence for the mRNA vaccines are synthetic oligonucleotides*. Since mRNA is not very stable, the genetic materials include modified nucleosides to prevent degradation.5 Moreover, mRNA is highly vulnerable to degradation by enzymes, called extracellular RNases, in our body. Therefore, mRNAs of the mRNA vaccines are usually encapsulated within lipids or polymeric nanoparticles to protect the mRNAs and to enable entry of the mRNA into cells. These carrier systems are designed to protect mRNA from enzymes' degradation and also allow rapid uptake of the mRNA by human cells.3,6 Recent technology innovations, especially in nanotechnology, enables the synthesis of mRNA molecules with higher stability and the encapsulation of mRNA molecules in nanoparticles for efficient delivery of mRNA into target cells.5
Additionally, in order to provoke a stronger immune response, a booster shot is usually added after the first shot of the mRNA vaccine. The two mRNA vaccine candidates for COVID-19 that have entered phase 3 clinical trials both require 2 doses.
Advantages of mRNA vaccines over conventional vaccines
1. Faster and cheaper to produce: The process of producing mRNA is inexpensive, and could be standardised and scaled easily. This allows quick responses to large outbreaks and epidemics.3
2. Higher efficacy: There is no viral vector to carry mRNA, therefore the anti-vector immunity, which could decrease the efficacy of the vaccine, is avoided. Additionally, as there is no fear of anti-vector immunity, mRNA vaccines can be administered repeatedly.3
3. Safer: mRNA vaccine does not contain any viral component, neither inactivated disease-causing organisms or proteins made by pathogen. Thus there is no potential risk of infection or insertional mutagenesis. Moreover, mRNA is degraded by normal cellular processes, and its in vivo half-life can be regulated through the use of various modifications and delivery methods. The inherent immunogenicity of the mRNA can be down-modulated to further increase the safety profile.3
However, since mRNA vaccine is a new type of vaccine developed by new technology, it has never before been applied clinically. It is now too early to say the vaccine is totally safe. Long-term follow-up over many years on the people who have used mRNA vaccines is necessary to find out if there are any long-term side effects of this type of vaccine.
Both of the mRNA vaccine candidates for COVID-19 contain genetic codes for the Spike glycoprotein of SARS-CoV-2. My next two blog posts will take a closer look at the two mRNA vaccine candidates.
*Synthesized oligonucleotides are short fragments of nucleic acids with defined chemical structure manufactured by biotech companies. The technique of synthesizing oligonucleotides is very useful, as it provides a convenient and inexpensive way to produce custom-made fragments of nucleic acids with desired sequences.
References
1. Decision: Regulatory approval of Pfizer/ BioNTech vaccine for COVID-19. Gov.UK’s news release, 2nd Dec, 2020. https://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19
2. Draft landscape of COVID-19 candidate vaccines. World Health Orgainzation. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
3. N. Pardi, M.J. Hogan, F.W. Porter, et al. mRNA vaccines — a new era in vaccinology. Nat. Rev. Drug Discov. 2018 Apr; 17(4):261-279.
4. Behind the science: what is an mRNA vaccine? Pfizer's website. https://www.pfizer.co.uk/behind-science-what-mrna-vaccine
5. K. Kariko, H. Muramatsu, F.A. Welsh, et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther., 2008, 16(11), 1833–1840.
6. How nanotechnology helps mRNA Covid-19 vaccines work. By Elizabeth Cooney. STAT Biotech, 1st Dec., 2020. https://www.statnews.com/2020/12/01/how-nanotechnology-helps-mrna-covid19-vaccines-work/
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