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SARS-CoV-2 Vaccines: An Introduction
- 3. Human cell Body ACE2 Receptor In Vitro Spike Protein M Protein RNA Coronavirus Viral RNA translated into proteins Virus enters the body 1. Vesicle Virus enters a cell 2. Virus fuses with vesicle and its RNA is released 3. Virus assembly 4. Virus release 5. The virus uses its surface spike protein to lock onto ACE2 receptors on the surface of human cells. Once inside, these cells translate the virus’s RNA to produce more viruses. Coronavirus Infection SARS-CoV-2 Introduction - Virus Infection
- 4. Virus ingested by antigen- presenting cell (APC) T-helper Cell B Cell Cytotoxic T cell Anti-coronavirus Antibody Long-lived memory B and T cells that recognize the virus can protect the body for months or years, providing immunity. Destroy infected cells Viral Peptide Specialized antigen-presenting cells engulf the virus and display portions of it to activate T-helper cells. Immune response T-helper cells enable other immune responses: B cells make antibodies that can block the virus from infecting cells, as well as mark the virus for destruction. Cytotoxic T cells identify and destroy virus-infected cells. SARS-CoV-2 Introduction - Immune Response Memory Cells MHCⅡ
- 5. 0 R&D CLINICAL LOGISTICS SARS-CoV-2 Vaccines Introduction - Vaccine Development Platform choice E.g. proper Spike trimer formation, folding and glycan structure (Protein), generation of neutralizing Abs, excellent expression (DNA, RNA), Efficient cell transduction (Viral vector), etc. Neutralizing Abs, robust and appropriate T-cell activation and cytokines, SARS-Cov-2 viral killing in challenge studies, protection from COVID symptoms. PhaseⅠ Ø Safety Idea vaccine Ø Billions of doses Ø Elicits effective， long-lasting immunity Manufacturing capabilities Side-effects Ø Reaction site/systemic Aes Ø ADE, ADCC, CDC, VAERD Lack of efficacy Ø Minimal/no protection Design 1-5 target Prep small batches In vitro testing Targeting selection Target validation Ø SARS-CoV-2 infection assays Vero cells Ø Positive T-cell response Preclinical testing in vitro in cell culture and in vivo in animals Phase Ⅱ Ø Safety Ø Efficacy Phase Ⅲ Ø Efficacy Ø Protection COVID-19 Scale up Worldwide distribution Storage Supply chain
- 6. All vaccines aim to expose the body to an antigen that won’t cause disease, but will provoke an immune response that can block or kill the virus if a person becomes infected. There are at least eight types being developed against the coronavirus, and they are based on different viruses or viral parts. Virus Viral Vector Nucleic Acid Protein-based Others 0 5 10 15 20 25 30 35 Number of vaccines in development SARS-CoV-2 Vaccines Introduction - Vaccine Types Virus Inactivated Weakened Protein-based Protein subunit Virus-like particles Viral Vector Replicating Non-replicating Nucleic Acid DNA RNA
- 7. Antigen-presenting Cell Cell Immune Respons e or Weakened Virus Inactivated Virus Vaccine Virus Replicates Coronavirus Peptide SARS-CoV-2 Vaccines Introduction - Virus Vaccines
- 8. Antigen-presenting Cell Immune Response Cell Coronavirus Spike Peptide Virus Replicates or Vaccine Replicating Viral Vector Viral Genes Coronavirus Spike Gene Non-replicating Viral Viral Genes (some inactive) Coronavirus Spike Gene Replicating Viral Vector (such as Weakened Measles) Non-replicating Viral Vector (such as Adenovirus) SARS-CoV-2 Vaccines Introduction - Viral Vector Vaccines Vaccine
- 9. Cell Nucleus Immune Response Coronavirus Spike Peptide Coronavirus Spike Gene DNA Electroporation DNA Vaccine RNA Vaccine RNA RNA is often encased in a lipid coat so it can enter cells Viral Proteins mRNA RNA- and DNA-based vaccines are safe and easy to develop. The production only involves making genetic material, not the virus. But this method is unproven since no licensed vaccines use this technology. A process called electroporation creates pores in membranes to increase uptake of DNA into a cell. SARS-CoV-2 Vaccines Introduction - Nucleic Acid Vaccines
- 10. Coronavirus Peptide Protein Subunits Virus-like Particles Immune Response VLP Immune Response Coronavirus Peptide Spike protein M protein SARS-CoV-2 Vaccines Introduction - Protein-based Vaccines
- 11. Advantages/Disadvantages of SARS-CoV-2 Vaccines Virus Vaccine Direct immune response No adjuvant required No need to purify antigen protein High storage conditions Effectiveness and risk are not balanced Viral Vector Vaccine Without adjuvant Strong security Strong immune response Weaken vaccine effectiveness High transportation and storage requirements Protein-based Vaccine Simple ingredients Easy quality control Need adjuvant Need multiple injections Long development cycle Advantages Disadvantages Advantages Disadvantages Advantages Disadvantages Nucleic Acid Vaccine Good stability Security and easy development Low cost Unknown side effects Advantages Disadvantages
- 12. SARS-CoV-2 Vaccine Pipeline 199 vaccines are in development 19 vaccines are in clinical testing Note: Ⅰ Ⅱ Ⅲ RR https://www.covid-19vaccinetracker.org/
- 13. • In Silico Vaccine Design for SARS-CoV- 2 • Live Attenuated and Killed Vaccine Development Services for SARS-CoV-2 • Recombinant Subunit Vaccine Development Services for SARS-CoV-2 • mRNA Vaccine Development Services for SARS-CoV-2 • Modified Vaccinia Virus Vectored Vaccine Development Services for SARS- CoV-2 • Virus-Like Particles Based Vaccine Development Services for SARS-CoV-2 • Formulation Optimization Platform for SARS-CoV-2 Vaccine • Analysis & Qualification Service for SARS-CoV-2 Vaccine Creative Biolabs’ Services
- 14. Drug Discovery Services In Vitro Diagnostic (IVD) Development • Anti-SARS-CoV-2 Drug Discovery • Antibody & Immunoassay Development Services • SARS-CoV-2 Vaccine Discovery • SARS-CoV-2 Preclinical Research • Molecular Diagnostic Assay Development Services • SARS-CoV-2 Related Detection Kits Creative Biolabs’ Services
- 15. Phone: 1-631-466-5530 Web: www.creative-biolabs.com Email: info@creative-biolabs.com Address: 45-1 Ramsey Road, Shirley, NY 11967, USA