DOCSLIB.ORG

Comirnaty, INN-COVID-19 Mrna Vaccine (Nucleoside-Modified)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comirnaty, INN-COVID-19 Mrna Vaccine (Nucleoside-Modified) 19 February 2021 EMA/707383/2020 Corr.1*1 Committee for Medicinal Products for Human Use (CHMP) Assessment report Comirnaty Common name: COVID-19 mRNA vaccine (nucleoside-modified) Procedure No. EMEA/H/C/005735/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 1 * Correction dated 19 February 2021 to clarify ERA statement Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us An agency of the European Union Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 8 1.1. Submission of the dossier ...................................................................................... 8 1.2. Steps taken for the assessment of the product ......................................................... 9 2. Scientific discussion .............................................................................. 11 2.1. Problem statement ............................................................................................. 11 2.1.1. Disease or condition ......................................................................................... 11 2.1.2. Epidemiology and risk factors ............................................................................ 11 2.1.3. Aetiology and pathogenesis .............................................................................. 11 2.1.4. Clinical presentation and diagnosis .................................................................... 12 2.1.5. Management ................................................................................................... 13 2.2. Quality aspects .................................................................................................. 14 2.2.1. Introduction .................................................................................................... 14 2.2.2. Active Substance ............................................................................................. 15 2.2.3. Finished Medicinal Product ................................................................................ 22 2.2.4. Discussion on chemical, pharmaceutical and biological aspects .............................. 31 2.2.5. Conclusions on the chemical, pharmaceutical and biological aspects ...................... 35 2.2.6. Recommendations for future quality development................................................ 39 2.3. Non-clinical aspects ............................................................................................ 41 2.3.1. Pharmacology ................................................................................................. 41 2.3.2. Pharmacokinetics............................................................................................. 45 2.3.3. Toxicology ...................................................................................................... 48 2.3.4. Ecotoxicity/environmental risk assessment ......................................................... 51 2.3.5. Discussion on non-clinical aspects...................................................................... 51 2.3.6. Conclusion on the non-clinical aspects ................................................................ 55 2.4. Clinical aspects .................................................................................................. 56 2.4.1. Introduction .................................................................................................... 56 2.4.2. Pharmacokinetics............................................................................................. 58 2.4.3. Pharmacodynamics .......................................................................................... 58 2.4.4. Discussion on clinical pharmacology ................................................................... 66 2.4.5. Conclusions on clinical pharmacology ................................................................. 67 2.5. Clinical efficacy .................................................................................................. 67 2.5.1. Dose response study ........................................................................................ 67 2.5.2. Main study ...................................................................................................... 67 2.5.3. Discussion on clinical efficacy ............................................................................ 92 2.5.4. Conclusions on clinical efficacy .......................................................................... 97 2.6. Clinical safety .................................................................................................... 98 2.6.1. Patient exposure ............................................................................................. 99 2.6.2. Reactogenicity ............................................................................................... 101 2.6.3. Adverse events ............................................................................................. 103 2.6.4. Serious adverse event/deaths/other significant events ....................................... 108 2.6.5. Laboratory findings ........................................................................................ 109 2.6.6. Safety in special populations ........................................................................... 109 2.6.7. Safety related to drug-drug interactions and other interactions ........................... 110 Assessment report EMA/707383/2020 Page 2/140 2.6.8. Discontinuation due to adverse events ............................................................. 110 2.6.9. Post marketing experience .............................................................................. 110 2.6.10. Discussion on clinical safety .......................................................................... 111 2.6.11. Conclusions on the clinical safety ................................................................... 114 2.7. Risk Management Plan ...................................................................................... 115 Safety Specification ................................................................................................. 115 Pharmacovigilance Plan ........................................................................................... 116 Routine pharmacovigilance activities ......................................................................... 116 Additional pharmacovigilance activities ...................................................................... 118 Overall conclusions on the Pharmacovigilance Plan ...................................................... 122 Plans for post-authorisation efficacy studies ............................................................... 122 Risk minimisation measures ..................................................................................... 123 Routine Risk Minimisation Measures .......................................................................... 123 Summary of additional risk minimisation measures ..................................................... 123 Overall conclusions on risk minimisation measures ...................................................... 126 Summary of the risk management plan ..................................................................... 127 Conclusion on the RMP ............................................................................................ 127 2.8. Pharmacovigilance ............................................................................................ 127 2.9. Product information .......................................................................................... 127 2.9.1. User consultation ........................................................................................... 127 2.9.2. Labelling exemptions ..................................................................................... 127 2.9.3. Quick Response (QR) code .............................................................................. 129 2.9.4. Additional monitoring ..................................................................................... 129 3. Benefit-Risk Balance............................................................................ 130 3.1. Therapeutic Context ......................................................................................... 130 3.1.1. Disease or condition ....................................................................................... 130 3.1.2. Available therapies and unmet medical need ..................................................... 130 3.1.3. Main clinical studies ....................................................................................... 130 3.2. Favourable effects ............................................................................................ 131 3.3. Uncertainties and limitations about favourable effects ........................................... 132 3.4. Unfavourable effects ......................................................................................... 132 3.5. Uncertainties and limitations about unfavourable effects ....................................... 133 3.6. Effects Table ...................................................................................................
Load more

Recommended publications
  • Main Outcomes of Discussion of WHO Consultation on Nucleic Acid
    MAIN OUTCOMES OF DISCUSSION FROM WHO CONSULTATION ON NUCLEIC ACID VACCINES I. Knezevic, R. Sheets 21-23 Feb, 2018 Geneva, Switzerland CONTEXT OF DISCUSSION • WHO Consultation held to determine whether the existing DNA guidelines were due for revision or if they remained relevant with today’s status of nucleic acid vaccine development and maturity towards licensure (marketing authorization) • Presentation will cover alignment to existing guidelines • Current status of development of DNA and RNA vaccines, both prophylactic & therapeutic • Main outcomes of discussion • Next steps already underway & planned STATUS OF DEVELOPMENT OF NUCLEIC ACID VACCINES • First likely candidate to licensure could be a therapeutic DNA vaccine against Human Papilloma Viruses • Anticipated to be submitted for licensure in 3-5 years • Other DNA vaccines are likely to follow shortly thereafter, e.g., Zika prophylaxis • RNA vaccines – less clinical experience, but therapeutic RNAs anticipated in 2021/22 timeframe to be submitted for licensure • For priority pathogens in context of public health emergencies, several candidates under development (e.g., MERS-CoV, Marburg, Ebola) MAIN OUTCOMES - GENERAL • Regulators expressed need for updated DNA guideline for prophylaxis and therapy • Less need at present for RNA vaccines in guideline but need some basic PTC • Flexibility needed now until more experience gained for RNA vaccines that will come in next few years • Revisit need for a more specific guideline at appropriate time for RNA vaccines • Institutional Biosafety Committees are regulated by national jurisdictions & vary considerably • How can WHO assist to streamline or converge these review processes? Particularly, during Public Health Emergency – can anything be done beforehand? MAIN OUTCOMES - DEFINITIONS • Clear Definitions are needed • Proposed definition of DNA vaccine: • A DNA plasmid(s) into which the desired immunogen(s) is (are) encoded and prepared as purified plasmid preparations to be administered in vivo.
    [Show full text]
  • Rnase a Cleanup of DNA Samples Version Number: 1.0 Version 1.0 Date: 12/21/2016 Author(S): Yuko Yoshinaga, Eileen Dalin Reviewed/Revised By
    SAMPLE MANAGEMENT STANDARD OPERATING PROCEDURE RNase A Cleanup of DNA Samples Version Number: 1.0 Version 1.0 Date: 12/21/2016 Author(s): Yuko Yoshinaga, Eileen Dalin Reviewed/Revised by: Summary RNase A treatment is used for the removal of RNA from genomic DNA samples. RNase A cleaves the phosphodiester bond between the 5'-ribose of a nucleotide and the phosphate group attached to the 3'- ribose of an adjacent pyrimidine nucleotide. The resulting 2', 3'-cyclic phosphate is hydrolyzed to the corresponding 3'-nucleoside phosphate. Materials & Reagents Materials Vendor Stock Number Disposables 1.5 ml microcentrifuge tubes Reagents TE Buffer, pH 8.0 Ambion 9849 RNase A, DNase and protease-free (10 mg/ml) ThermoFisher EN0531 Sodium acetate buffer solution (3M, pH 5.2) VWR 567422 Ethanol, 200 proof Pharmco-Aaper 111000200CSPP 50x TAE Buffer Life Technologies/ Invitrogen MRGF-4210 SYBR® Safe DNA gel stain (10,000x concentrate in Life Technologies/ Invitrogen S33102 DMSO) DNA Molecular Weight Marker II Sigma 10236250001 Gel Loading Dye, Blue (6x) New England BioLabs B7021S Equipment Centrifuge 4°C Heat block 37°C Gel electrophoresis device Gel Imager Bio-Rad EH&S PPE Requirements: 1.1 Safety glasses, lab coat, and nitrile gloves should be worn at all times while performing work in the lab during this protocol. 1.2 Ethanol is a highly flammable and irritating to the eyes. Vapors may cause drowsiness and dizziness. Keep containers closed and keep away from sources of ignition such as smoking. 1 SAMPLE MANAGEMENT STANDARD OPERATING PROCEDURE Avoid contact with skin and eyes. In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
    [Show full text]
  • Review of COVID-19 Vaccine Subtypes, Efficacy and Geographical Distributions Andre Ian Francis ‍ ‍ ,1 Saudah Ghany,1 Tia Gilkes,1 Srikanth Umakanthan2
    Review Postgrad Med J: first published as 10.1136/postgradmedj-2021-140654 on 6 August 2021. Downloaded from Review of COVID-19 vaccine subtypes, efficacy and geographical distributions Andre Ian Francis ,1 Saudah Ghany,1 Tia Gilkes,1 Srikanth Umakanthan2 1Department of Clinical Medical ABSTRACT 2021, the Ad26.COV2.S, developed by Janssen Sciences, The Faculty of Medical As of 1 May 2021, there have been 152 661 445 (Johnson & Johnson) and Moderna on 30 April.4 Sciences, The University of the COVAX, coordinated by WHO, Gavi: The West Indies, St. Augustine, Covid-19 cases with 3 202 256 deaths globally. Trinidad and Tobago This pandemic led to the race to discover a vaccine Vaccine Alliance, the Coalition for Epidemic 2Pathology unit, Department to achieve herd immunity and curtail the damaging Preparedness Innovations (CEPI), acts as a of Paraclinical Sciences, The effects of Covid-19. This study aims to discuss the most programme that supports the development of University Of The West Indies, St. COVID-19 vaccine candidates and negotiates their Augustine, Trinidad and Tobago recent WHO-approved Covid-19 vaccine subtypes, their status and geographical scheduled updates as of 4 pricing to ensure low- and- middle- income countries have a fair shot at receiving vaccines.5 Correspondence to May 2021. The keywords “Covid-19, Vaccines, Pfizer, Mr. Andre Ian Francis, The BNT162b2, AstraZeneca, AZD1222, Moderna, mRNA- This article aims at discussing the most recent University of the West Indies, St. 1273, Janssen, Ad26.COV2.S” were typed into PubMed. WHO- approved COVID-19 vaccine subtypes, their Augustine, Trinidad and Tobago; Thirty Two relevant PubMed articles were included in status and geographical scheduled updates as of 4 andre.
    [Show full text]
  • Secretariat of the CBD Technical Series No. 82 Convention on Biological Diversity
    Secretariat of the CBD Technical Series No. 82 Convention on Biological Diversity 82 SYNTHETIC BIOLOGY FOREWORD To be added by SCBD at a later stage. 1 BACKGROUND 2 In decision X/13, the Conference of the Parties invited Parties, other Governments and relevant 3 organizations to submit information on, inter alia, synthetic biology for consideration by the Subsidiary 4 Body on Scientific, Technical and Technological Advice (SBSTTA), in accordance with the procedures 5 outlined in decision IX/29, while applying the precautionary approach to the field release of synthetic 6 life, cell or genome into the environment. 7 Following the consideration of information on synthetic biology during the sixteenth meeting of the 8 SBSTTA, the Conference of the Parties, in decision XI/11, noting the need to consider the potential 9 positive and negative impacts of components, organisms and products resulting from synthetic biology 10 techniques on the conservation and sustainable use of biodiversity, requested the Executive Secretary 11 to invite the submission of additional relevant information on this matter in a compiled and synthesised 12 manner. The Secretariat was also requested to consider possible gaps and overlaps with the applicable 13 provisions of the Convention, its Protocols and other relevant agreements. A synthesis of this 14 information was thus prepared, peer-reviewed and subsequently considered by the eighteenth meeting 15 of the SBSTTA. The documents were then further revised on the basis of comments from the SBSTTA 16 and peer review process, and submitted for consideration by the twelfth meeting of the Conference of 17 the Parties to the Convention on Biological Diversity.
    [Show full text]
  • U6 Small Nuclear RNA Is Transcribed by RNA Polymerase III (Cloned Human U6 Gene/"TATA Box"/Intragenic Promoter/A-Amanitin/La Antigen) GARY R
    Proc. Nati. Acad. Sci. USA Vol. 83, pp. 8575-8579, November 1986 Biochemistry U6 small nuclear RNA is transcribed by RNA polymerase III (cloned human U6 gene/"TATA box"/intragenic promoter/a-amanitin/La antigen) GARY R. KUNKEL*, ROBIN L. MASERt, JAMES P. CALVETt, AND THORU PEDERSON* *Cell Biology Group, Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545; and tDepartment of Biochemistry, University of Kansas Medical Center, Kansas City, KS 66103 Communicated by Aaron J. Shatkin, August 7, 1986 ABSTRACT A DNA fragment homologous to U6 small 4A (20) was screened with a '251-labeled U6 RNA probe (21, nuclear RNA was isolated from a human genomic library and 22) using a modified in situ plaque hybridization protocol sequenced. The immediate 5'-flanking region of the U6 DNA (23). One of several positive clones was plaque-purified and clone had significant homology with a potential mouse U6 gene, subsequently shown by restriction mapping to contain a including a "TATA box" at a position 26-29 nucleotides 12-kilobase-pair (kbp) insert. A 3.7-kbp EcoRI fragment upstream from the transcription start site. Although this containing U6-hybridizing sequences was subcloned into sequence element is characteristic of RNA polymerase II pBR322 for further restriction mapping. An 800-base-pair promoters, the U6 gene also contained a polymerase III "box (bp) DNA fragment containing U6 homologous sequences A" intragenic control region and a typical run of five thymines was excised using Ava I and inserted into the Sma I site of at the 3' terminus (noncoding strand). The human U6 DNA M13mp8 replicative form DNA (M13/U6) (24).
    [Show full text]
  • V.5 3/18/2021 1 COVID-19 Vaccine FAQ Sheet
    COVID-19 Vaccine FAQ Sheet (updated 3/18/2021) The AST has received queries from transplant professionals and the community regarding the COVID-19 vaccine. The following FAQ was developed to relay information on the current state of knowledge. This document is subject to change and will be updated frequently as new information or data becomes available. What kinds of vaccines are available or under development to prevent COVID-19? There are currently several vaccine candidates in use or under development. In the United States, the Government is supporting six separate vaccine candidates. Several other vaccines are also undergoing development outside of the United States government sponsorship and further information can be found here: NYTimes Coronavirus Vaccine Tracker: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine- tracker.html Washington Post Vaccine Tracker: https://www.washingtonpost.com/graphics/2020/health/covid-vaccine-update- coronavirus/ v.5 3/18/2021 1 The types of vaccines are as follows (March 1, 2021) 1: Table 1: Vaccines Under Development or Available Through EUA Vaccine Type Compound Name [Sponsor] Clinical Notes Trial Phase mRNA mRNA-1273 [Moderna] Phase 3 Emergency use in U.S., E.U., other countries Approved in Canada BNT162b2 (Comirnaty) [Pfizer] Phase 2/3 Emergency use in U.S., E.U., other countries Also approved in Canada and other countries Replication- AZD1222 (Covishield) Phase 2/3 Emergency use defective [AstraZeneca] in U.K., India, adenoviral other countries vector (not U.S.) JNJ-78326735/Ad26.COV2.S
    [Show full text]
  • IL-10 and ICOS Differentially Regulate T Cell Responses in the Brain During Chronic 2 Toxoplasma Gondii Infection 3
    bioRxiv preprint doi: https://doi.org/10.1101/418665; this version posted September 15, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 IL-10 and ICOS differentially regulate T cell responses in the brain during chronic 2 Toxoplasma gondii infection 3 4 Carleigh A. O’Brien*, Samantha J. Batista*, Katherine M. Still*, and Tajie H. Harris* 5 6 Affiliations: *Center for Brain Immunology and Glia, Department of Neuroscience, University of 7 Virginia, Charlottesville, VA 22908 8 9 Corresponding Author: 10 Tajie H. Harris, MR-4 Room 6148, 409 Lane Road, Charlottesville, VA 22908 11 Phone: 434-982-6916 12 Fax: 434-9824380 13 Email: [email protected] 14 15 This work was funded by the National Institutes of Health grants R01NS091067 to T.H.H., 16 T32AI007496 to C.A.O, T32AI007046 to S.J.B., and T32GM008328 to K.M.S., as well as the 17 University of Virginia Robert R. Wagner Fellowship to C.A.O. 18 19 20 21 22 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/418665; this version posted September 15, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 25 Abstract 26 Control of chronic CNS infection with the parasite Toxoplasma gondii requires an ongoing T cell 27 response in the brain. Immunosuppressive cytokines are also important for preventing lethal 28 immunopathology during chronic infection.
    [Show full text]
  • Third Quarter 2020
    March 31, 2020 Third Quarter 2020 Corporate update and financial results November 10, 2020 Forward-looking statements Various statements in this slide presentation concerning the future expectations of BioNTech, its plans and prospects, including the Company's views with respect to the potential for mRNA and other pipeline therapeutics; BioNTech's efforts to combat COVID-19; the collaborations between BioNTech and Pfizer and Fosun to develop a potential COVID-19 vaccine; our expectations regarding the potential characteristics of BNT162b2 in our continuing Phase 2/3 trial and/or in commercial use based on data observations to date; the expected timepoint for additional readouts on efficacy data of BNT162b2 in our Phase 2/3 trial; the nature of the clinical data for BNT162, BNT311 and our other product candidates, which is subject to ongoing peer review, regulatory review and market interpretation; the timing for submission of data for, or receipt of, any potential approval or Emergency Use Authorization with respect to our BNT162 program; the timing for submission of BNT162 manufacturing data to the FDA; the ability of BioNTech to supply the quantities of BNT162 to support clinical development and, if approved, market demand, including our production estimates for 2020 and 2021 and orders received to-date; the planned next steps in BioNTech's pipeline programs and specifically including, but not limited to, statements regarding plans to initiate clinical trials of BioNTech's product candidates and expectations for data announcements with
    [Show full text]
  • Certain Tadalafil Or Any Salt Solvate Thereof and Products Containing
    In the Matter of Certain Tadalafil or any Salt or Solvate Thereof and Products Containing Same Investigation No. 337-TA-539 Publication 3992 May2008 U.S. International Trade Commission Washington, i::>C 20436 U.S. International Trade Commission COMMISSIONERS Daniel R. Pearson, Chairman Shara L. Aranoff, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson* Dean A. Pinkert* *Coirmissioner Marcia E. Miller, whose term ended on September 6, 2005, participated in the decision to institute the investigation. Commissioner Shara L. Aranoff, whose term commenced on September 6, 2005, participated in all subsequent phases of the investigation. Commissioner Irving A. Williamson was sworn in on February 7, 2007, and Commissioner Dean A. Pinkert was sworn in on February 26, '2007; they did not participate in this investigation. Commissioner Stephen Koplan, whose term ended on February 6, 2007, and Commissioner Jennifer A. Hillman, whose term ended on February 23, 2007, did participate in this investigation. ' Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov In the Matter of Certain Tadalafil or any Salt or Solvate Thereof and Products Containing Same Investigation No. 337-TA-539 Publication 3992 May 2008 UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. 20436 ) In the Matter of ) ) CERTAIN TADALAFIL OR ANY SALT OR ) Inv. No. 337-TA-539 SOLVATETHEREOFANDPRODUCTS ) CONTAINING SAME ) ~~~~~~~~~~~~~~~~~> NOTICE OF COMMISSION ISSUANCE OF GENERAL EXCLUSION ORDER; DECISION TO GRANT MOTION TO FILE A SURREPLY; TERMINATION OF THE INVESTIGATION AGENCY: U.S. International Trade Commission.
    [Show full text]
  • Bristol-Myers Squibb 2019 Annual Report
    We’re inspired by a single vision: 2019 ANNUAL REPORT Our Mission To discover, develop and deliver innovative medicines that help patients prevail over serious diseases Our Vision To be the world's leading biopharma company that transforms patients' lives through science The patient stories shared in this Annual Report depict individual patient responses to our medicines or investigational compounds and are not representative of all patient responses. In addition, there is no guarantee that potential drugs or indications still in development will receive regulatory approval. Bristol Myers Squibb 2019 Annual Report Myers Bristol Made Strong® is a registered mark of the Made Strong organization. Used with permission. Letter from the Chairman and CEO At Bristol Myers Squibb, we are inspired by our mission – to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. Every day, we focus on innovations that drive meaningful breakthroughs so we can bring life-saving medicines to people around the world. 2019 was a transformative year for us. A BIOPHARMA LEADER THE POWER OF FOLLOWING THE SCIENCE The acquisition of Celgene Corporation significantly We start this next chapter at a time when unprecedented advanced our strategy to create a leading biopharma scientific breakthroughs are advancing the treatment company by bringing together the speed and agility of disease as never before. Bristol Myers Squibb is well of a biotech with the global scale and resources of an positioned in scientific hubs of innovation in the U.S. and established pharmaceutical company. Our new company globally, and we collaborate with a broad network of global has strong commercial franchises in oncology, hematology, partners across our disease areas of focus to sustain our immunology and cardiovascular disease, one of the most leadership and continue to transform patient outcomes.
    [Show full text]
  • Expanding the Genetic Code Lei Wang and Peter G
    Reviews P. G. Schultz and L. Wang Protein Science Expanding the Genetic Code Lei Wang and Peter G. Schultz* Keywords: amino acids · genetic code · protein chemistry Angewandte Chemie 34 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/anie.200460627 Angew. Chem. Int. Ed. 2005, 44,34–66 Angewandte Protein Science Chemie Although chemists can synthesize virtually any small organic molecule, our From the Contents ability to rationally manipulate the structures of proteins is quite limited, despite their involvement in virtually every life process. For most proteins, 1. Introduction 35 modifications are largely restricted to substitutions among the common 20 2. Chemical Approaches 35 amino acids. Herein we describe recent advances that make it possible to add new building blocks to the genetic codes of both prokaryotic and 3. In Vitro Biosynthetic eukaryotic organisms. Over 30 novel amino acids have been genetically Approaches to Protein encoded in response to unique triplet and quadruplet codons including Mutagenesis 39 fluorescent, photoreactive, and redox-active amino acids, glycosylated 4. In Vivo Protein amino acids, and amino acids with keto, azido, acetylenic, and heavy-atom- Mutagenesis 43 containing side chains. By removing the limitations imposed by the existing 20 amino acid code, it should be possible to generate proteins and perhaps 5. An Expanded Code 46 entire organisms with new or enhanced properties. 6. Outlook 61 1. Introduction The genetic codes of all known organisms specify the same functional roles to amino acid residues in proteins. Selectivity 20 amino acid building blocks. These building blocks contain a depends on the number and reactivity (dependent on both limited number of functional groups including carboxylic steric and electronic factors) of a particular amino acid side acids and amides, a thiol and thiol ether, alcohols, basic chain.
    [Show full text]
  • An Update on Self-Amplifying Mrna Vaccine Development
    Review An Update on Self-Amplifying mRNA Vaccine Development Anna K. Blakney 1,* , Shell Ip 2 and Andrew J. Geall 2 1 Michael Smith Laboratories, School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z4, Canada 2 Precision NanoSystems Inc., Vancouver, BC V6P 6T7, Canada; [email protected] (S.I.); [email protected] (A.J.G.) * Correspondence: [email protected] Abstract: This review will explore the four major pillars required for design and development of an saRNA vaccine: Antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). We report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects. Keywords: RNA; self-amplifying RNA; replicon; vaccine; drug delivery 1. Introduction: The Four Pillars of saRNA Vaccines In December 2019, the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus emerged, causing a respiratory illness, coronavirus disease 2019 (COVID-19), in Hubei province, China [1,2]. The virus has spread globally, with the World Health Organization (WHO) declaring it a Public Health Emergency of International concern on 30 January 2020 and a pandemic officially on 7 March 2020 [3]. There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic [4]. There has been an unprecedented research effort and global Citation: Blakney, A.K.; Ip, S.; Geall, coordination which has resulted in the rapid development of vaccine candidates and A.J. An Update on Self-Amplifying initiation of human clinical trials.
    [Show full text]