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COVID-19 VACCINES IN CANADADr. Marina Salvadori and Dr. April Killikelly1
Declaration of Interests: Dr. Marina Salvadori- Nothing to declareDr. April Killikelly- Nothing to declare2
OBJECTIVES To describe SARS-CoV-2 spike protein as a vaccine antigen To discuss the similarities and differences between vaccine platformtechnologies that may be available in Canada3
SARS-COV-2 VACCINE ANTIGENS:THE SPIKE PROTEIN4
SARS-CoV-2 the virus that causes COVID-19SpikeNucleocapsid (N)Membrane (M)Envelope (E)ssRNA ( )SARS-CoV-2 Spike is a viral protein antigen on the surface of SARSCOV-2(L) Image: Transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patientin the U.S. Source: National Institutes of Health(R) Image: de Andrade Santos et al, Review in Frontiers in Microbiology Aug 20205
Spike mediates SARS-CoV-2 InfectionSpike (S) proteinSARS-CoV-2Anti-SpikeProteinAntibodyCell membraneACE-2 Host ReceptorInfection Spike mediates contact between the virus and the host cell to cause infection One way to prevent infection is to block the interaction between spike and ACE-2via the production of anti-spike antibodiesImage: Berkley Lights6
How to elicit anti-spike alinfectionSecondaryantibodyresponse Vaccination with spikeprotein elicits a primaryimmune response thatforms immunologicalmemory Upon natural infection,immunological memory iscalled upon to mount aprotective immuneresponseAntibody responseAcquiredimmunityTimeMemory cells formedImage: Modified from Janeway Immunobiology7
How to deliver SARS-CoV-2 spike protein:From Gene to ProteinProteinProteins are made through a 2step process:TranslationmRNAStep 2: Translation mRNA molecules aretranslated into proteinsTranscriptionDNAStep 1: Transcription Genes are transcribed intomRNAImage Adapted from Qin et al The Current Status and Challenges in Computational Analysis of Genomic Big Data8
How to deliver SARS-CoV-2 spike protein:From Gene to ProteinTranscriptionDNADifferent steps to create a proteinhappens in different locationswithin a cell: Transcription (DNA- mRNA)happens inside the nucleus ofthe cell Translation (mRNA- protein)happens inside the cytosol ofthe cellmRNATranslationImage Open Oregon StateWithout help, material does passinto the cytosol or the nucleus ofthe cell. Vaccine developers havedeveloped lipid nanoparticle andviral vector technology to allowDNA and mRNA to pass throughmembranes.9
VACCINE PLATFORMSProtein, mRNA and Viral Vector10
Vaccine Platforms Canada has made agreements in principle with 7 vaccinedevelopers to supply Canadians with doses of vaccine iftheir vaccine candidate is assessed to be safe andefficacious by Health Canada The vaccines in development for which Canada may havefirst access use three different technologies:– Protein subunit (including Virus Like Particles (VLPs))– Messenger RNA (mRNA)– Viral vectors11
Protein Subunit Vaccines:Subunit Protein Vaccines: Deliver vaccine antigens asproteins which directly elicit animmune response. An established technology Elicit a strong antibody response Commonly use adjuvants Generally slower manufacturingtimelinesCOVID-19 Protein Subunit vaccines:NovavaxSanofi12
Virus-Like Particle Vaccines (VLP)VLP Vaccines Deliver vaccine antigens asproteins which directly elicit animmune response. An established technology Elicit a strong antibody response Commonly use adjuvants Generally slower manufacturingtimelinesCOVID-19 VLP vaccines:MedicagoImage Micro and Nanotechnology in Vaccine Development13
Cellular andHumoral ImmuneResponsesMessenger RNA (mRNA) Vaccines:mRNAProteinmRNA-LNPmRNA Vaccines: Lipid nanoparticles are used to delivermRNA directly into cells mRNA coding for spike protein arethen translated New technology Elicitation of antibodies and T-cells Fast manufacturing timelinemRNA vaccines:ModernaPfizer/BioNTechImage: Opportunities and Challenges in the Delivery of mRNA-Based VaccinesProteinTranslationmRNA14
AdenovirusCOVID-19 Viral Vector VaccinesNon-ReplicatingVector VaccineCoronavirusspike RNA geneCoronavirusspike DNA geneHuman CellSARS-CoV-2NucleusViral Vector Vaccines: Modified adenovirus used as a vector todeliver spike genes (DNA) into the cell Elicitation of antibodies and T-cells Potential for interference from pre-existingadenoviral ID-19 VLP vaccines:Janssen/Johnson & JohnsonAstraZeneca/University of OxfordmRNA15
Assessing Vaccine Efficacy Vaccine Efficacy: How well a vaccine protects vaccinated vs unvaccinated people fromdisease in a clinical trialVaccine Effectiveness: How well a vaccine protects vaccinated vs unvaccinated peoplefrom disease in the real worldRandomized controlled trials (RCTs) are the best method to assess vaccine efficacyIncidence of Disease inPlacebo Group: (7/8)PlaceboPlaceboIncidence of Disease inVaccine Group: (1/8)Population is split into 2groups by random lotOutcomes for bothgroups are measuredVaccineVaccineHealthyHealthySickSickImage adapted from: Test, Learn, Adapt: Developing Public Policy with Randomised Controlled TrialsVaccine Efficacy:The vaccinated groupwould experience 86%fewer disease casesthan they would have ifthey had not beenvaccinated.16
Updated 2021-01-29COVID-19 Vaccine Development Landscape:Confirmed APA with CanadaVaccine Program TerminatedPreclinicalPhase IPhase IIPhase vavaxVBI Virus LikeMedicago iv of L/MorningPNIInovioDNAValneva/Dynavax Inactivated*APA or other agreements outlining vaccine supply in principle. Amounts listed here may cover multiple mechanisms of access.Developed by the Secretariat to the National Advisory Committee on Immunization (NACI)AuthorizedAuthorized
mRNA Vaccines: Moderna and Pfizer/BioNTechSARS-CoV-2Spike mRNA Vaccine antigen is mRNA coding for a gene forSARS-CoV-2 spike protein mRNA is very unstablemRNA Lipid Nanoparticle mRNA LNPs are made of two parts mRNA Lipids The lipids allow the mRNA to enter into the cell Like oil and water, lipids don’t mix well with waterso the mRNA lipid nanoparticle vaccines havespecial frozen and ultrafrozen storage and handlingrequirements (ie: no shaking).LipidsLipidsmRNAmRNAImage adapted from : Solid Lipid Nanoparticles: A Potential Approach for Dermal Drug Delivery18
Viral Vector Vaccine: AstraZeneca (Janssen/J&J) Vaccine antigen is DNA coding for a gene forSARS-CoV-2 spike protein DNA is more stable than RNA but can’t get into thecell or the nucleus without helpSARS-CoV-2Spike DNAViral Vectored VaccineLipidsAdenovirus Viral Vector Vaccines are made of two parts DNA Non-replicating vector virus (Adenovirus) Adenovirus carries the vaccine antigen DNA intothe cell and into the nucleus of the cell Adenoviruses are much more complex than lipidparticles and have features to allow them to bestable at higher temperatures (fridge or roomtemperature)DNAmRNA19
Protein-Based Vaccines: (Novavax, Sanofi) Vaccine antigen is the SARS-CoV-2 spike proteinSARS-CoV-2Spike ProteinProtein-based Vaccine Adjuvant Protein-based Vaccines can be made of two parts Protein antigen Adjuvant To elicit strong immune responses, protein-basedvaccines commonly use adjuvants Matrix M (Novavax) AS03 (Sanofi)20
Protein-Based Vaccines:Virus-Like Particle Vaccines (Medicago) Vaccine antigen is the SARS-CoV-2 spike protein Insertion at base of spike allow virus-like particle(VLP) formationSARS-CoV-2Spike Protein VLP Vaccines can be made of two parts Protein antigen in a VLP AdjuvantVLP Vaccines Adjuvant AS03 (Medicago)Image Micro and Nanotechnology in Vaccine Development21
Key Messages for COVID-19 Vaccine Candidates: SARS-CoV-2 spike protein antigens have been demonstrated to induceprotective efficacy against COVID-19 in randomized controlled trials Canada has negotiated agreements in principle to supply vaccine toCanadians with 7 companies who are using three different vaccineplatforms:– Protein subunit (including virus-like particle)– mRNA– Viral vector Different vaccine technology platforms use different methods to delivertheir antigen and may have different components, but they all aim todeliver the spike protein to elicit protective immune responses22
Additional ResourcesAuthorized COVID-19 vaccines in accines-treatments/vaccines.htmlCanadian Immunization es/canadian-immunizationguide.htmlNational Advisory Committee on Immunization -immunization-naci.html23
Image: Modified from Janeway Immunobiology 7 Vaccination Primary antibody response Natural infection Secondary antibody response Acquired immunity Time Memory cells formed e. How to deliver SARS-CoV-2 spike protein: From Gene to Protein Proteins are made through a 2 step process:
