Vaccines & Therapeutics BIOT 203 Fall 2023 PDF

Vaccines & Therapeutics IMMU N OL OGY | B IOT 203 FA L L 2 0 2 3 | W E E K 9 D R . JON AT H A N ME MME Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 1 Unit 8: Vaccines & Therapeutics TOPICS LEARNING OBJECTIVES Vaccines Assess the application of vaccines and adjuvants in immunology. Adjuvants Va...

Vaccines & Therapeutics IMMU N OL OGY | B IOT 203 FA L L 2 0 2 3 | W E E K 9 D R . JON AT H A N ME MME Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 1 Unit 8: Vaccines & Therapeutics TOPICS LEARNING OBJECTIVES Vaccines Assess the application of vaccines and adjuvants in immunology. Adjuvants Vaccine development Explore and describe current research in vaccine development. Therapeutics Fall 2021 | A. Karagiorgakis Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 2 Vaccines & Therapeutics Vaccine: Biological preparation that provides active acquired immunity to a particular disease ◦ An effective way to prevent and fight infectious diseases ◦ Influenza vaccine, diphtheria vaccine, chickenpox vaccine, etc. ◦ Worldwide eradication of smallpox and large restriction of diseases such as polio, measles, and tetanus Therapeutic agents: administered to treat infection or disease Prophylactic: prevent future infection, illness, disease Therapeutic: administered after infection, illness, or disease has occurred, target a particular type of cell Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 3 Terminology Antigen Antibody Active immunity Passive immunity Vaccination Immunization Fall 2023 | J.Memme • A live or inactivated substance (e.g., protein, polysaccharide) capable of producing an immune response • Protein molecules (immunoglobulin) produced by B lymphocytes to help eliminate an antigen • Protection produced by the person’s own immune system • Usually permanent • Protection transferred from another human or animal • Temporary protection that wanes with time • The process of administration of an antigen • The development of a specific immune response IMMUNOLOGY | BIOT 203 4 Monovalent & Multivalent Vaccines Monovalent vaccine • Designed to immunize against a single antigen or microbe • Measles vaccine, chicken-pox vaccine Multivalent vaccine • Designed to immunize against two or more strains of the same microbe, or against two or more microbes • Pentavalent vaccine against Diphtheria, Tetanus, Pertussis, HepB, and Hib Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 5 Vaccine Preventable Diseases Tetanus Diphtheria Pertussis (Whooping Cough) Hemophilis influenza type b (Hib) Polio Hepatitis A Hepatitis B Rotavirus Mumps Measles Rubella (German Measles) Varicella (Chickenpox) Pneumococcus Meningococcus Influenza Human Papilloma Virus (HPV) Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 6 Publicly Funded Immunization Schedules for Ontario (as of June 2022) Publicly funded vaccines may be provided only to eligible individuals and must be free of charge *** Schedules also exist for patients starting vaccination as adolescents, or adults. Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 7 VIDEO: What is Herd Immunity? https://youtu.be/cEn1PKyBUNc?si=UgFFZcr9JV9fyxCy Herd Immunity Besides protection of the individual, vaccination may also provide a degree of community protection ◦ The relative protection of a population group is achieved by reducing or breaking the chains of transmission of an infectious agent because most of the population is resistant to infection Most of population immunized/resistant ◦ disease still exists ◦ spread prevented by lack of available hosts Benefits of herd immunity ◦ Most diseases on the previous slide are rare ◦ Non-immunized person less likely to contact infected person By Tkarcher - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=56760604 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 8 VIDEO: Transmissible Viral Vaccines / Trends in Microbiology (The potential for deliberate surreptitious vaccination) https://www.youtube.com/watch?v=RAhl2COdTRE Herd Immunity The mechanisms of herd immunity Reproduction number* Herd immunity threshold 6-7 85% Airborne 12-18 83-94% Mumps Airborne droplet 4-7 75-86% Whooping cough Airborne droplet 12-17 92-94% Polio Fecal-oral route 5-7 80-86% Rubella Airborne droplet 5-7 83-85% Smallpox Social contact 6-7 83-85% COVID-19 Airborne droplet 1.01 Disease Transmission ◦ Direct protection of vaccines against disease or transmissible infection Diptheria Saliva Measles ◦ Indirect protection of non-recipients by virtue of surreptitious vaccination (e.g., spread of attenuated vaccines), passive antibody, or just reduced sources of transmission Level to achieve herd immunity depends on infectiousness of agent *Average number of secondary infections resulting from single index case Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 9 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 10 Contents of immunizing agents available for use in Canada Ingredients Antigen • recognized by the adaptive immune system to kill and form memory Adjuvant • stimulates a greater immune response • Aluminum gels/salts Residuals • vaccines prepared in eggs; not suitable for allergic persons (most influenza vaccines) • egg protein Stabilizers • stabilizes vaccines against heat, light, acidity, humidity • MSG (monosodium glutamate) Preservative • Preserves the integrity of the vaccine • Thiomerosal Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 By World Health Organization, CC BY-SA 3.0 IGO, CC BY-SA 3.0 igo, https://commons.wikimedia.org/w/index.php?curid=98863670 11 Immunologic Adjuvants Used with specific vaccine antigens to enhance the stimulation, magnitude, or strength of the antigen-specific immune response Provoke mild inflammation to attracts phagocytes and accelerate activation/antigen presentation to T-cells for development of specific adaptive immune response Aluminum salts AS01B Adjuvants in Canada AS04 MF59 https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-1-key-immunization-information/page-15-contents-immunizing-agents-available-use-canada.html Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 12 Types of Vaccines Image Credit: https://i1.wp.com/covid19.trackvaccines.org/wp-content/uploads/2021/08/Type-of-vaccines1.png?resize=766%2C431&ssl=1 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 13 Whole Virus Vaccines INACTIVATED LIVE-ATTENUATED Inactivated or killed vaccines Unable to replicate, infect, or function Promote weaker immune response than live vaccines ◦ Boosters and adjuvants Shelf-stable, freeze-dried, easily transportable Copies of the virus that have been weakened Low risk of infection ◦ Not appropriate for pathogens that can cause severe or life-threatening diseases or people who are immunocompromised Not possible for all organisms due to loss of ability to bind specifically to T-cell Provide life-long immunity Short shelf life Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 14 Component Viral Vaccines PROTEIN SUBUNIT Contains a purified component of the virus that will produce an immune response VIRUS-LIKE PARTICLES Synthetic protein structures that resemble viruses ◦ non-enveloped VLPs and enveloped VLPs Do not contain genetic material and are not infectious https://www.mayoclinic.org/-/media/kcms/gbs/patient-consumer/images/2021/10/05/15/20/covid-illustrations-antigen6-8col.jpg Fall 2023 | J.Memme https://www.creative-biolabs.com/vaccine/images/Enveloped-Virus-Like-Particle-Based-Vaccines-1.png IMMUNOLOGY | BIOT 203 15 Component Viral Vaccines DNA-BASED RNA-BASED DNA that has been extracted from the pathogen mRNA delivers ‘instructions’ to create viral proteins to promote an immune response ◦ Target: the genes that code for antigens Host cells take up the DNA and express gene products from the pathogens, mounting immune response ◦ Host cells make and display antigens https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/different-types-of-covid-19-vaccines/art-20506465#dialogId27793612 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 16 RNA Vaccine: Moderna’s mRNA Approach https://www.compoundchem.com/2020/12/02/rna-vaccines/ Fall 2023 | J.Memme https://www.modernatx.com/sites/default/files/moderna_vaccine_approach2.jpg IMMUNOLOGY | BIOT 203 17 Component Viral Vaccines Viral genetic material inserted into a harmless virus, which delivers ‘instructions’ to create viral proteins to promote an immune response Non-replicating viral vector: cannot copy Replicating viral vector: can copy https://www.mayoclinic.org/-/media/kcms/gbs/patient-consumer/images/2021/07/30/22/06/covid-illustrations-viral-vector-8col.jpg Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 18 1809 painting of patient experiencing muscle spasms associated with tetanus Toxoid Vaccines Some bacteria secrete toxins Toxin Organism Tetanus toxin Clostridium tetani Diphtheria toxin Corynebacterium diphtheriae Botulinum toxin Clostridium botulinum Pertussis toxin Bordetella pertussis Clostridial a-toxin Clostridial perfringens Cholera toxin Vibrio cholerae Anthrax toxin Bacillus anthracis Tetanus … and more DT: • Diphtheria and tetanus DTaP: • Diphtheria, tetanus, and pertussis Td: • Tetanus and diphtheria Tdap: • Tetanus, diphtheria, and pertussis Toxoid: inactivated toxins ◦ Toxin is treated with formalin and rendered inert Toxoid is harmless, but recognized by immune cells Public Domain, CC0 1.0 Universal, http://www.publicdomainpictures.net/view-image.php?image=77576&picture=vintage-diphtheria-poster Public Domain, CC0 1.0 Universal, http://www.publicdomainpictures.net/view-image.php?image=77576&picture=vintage-diphtheria-poste Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 19 Vaccine Development & Approval Clinical Trials Exploratory Preclinical Scientific Review Application Ongoing Monitoring & Review Distribution Approval Vaccination PDF summary: Vaccine development and approval in Canada (Health Canada) https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/development-approval-infographic/vaccine-overview-infographic-eng.pdf Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 20 Human Immunodeficiency Virus | HIV https://www.youtube.com/watch?v=hdgNnXLY8LU HIV ◦ Infects helper T-cells, macrophages, dendritic cells ◦ Reduces the number of Th cells ◦ Compromises the immune system Acquired Immune Deficiency Syndrome, AIDS ◦ Th cell blood count is less then 200,000 cells/mL ◦ Normal Th cell blood count: 500,000 to 1,400,000 cells/mL Lipid envelope Core ◦ transmembrane glycoprotein (GP41) ◦ Capsid protein (P24) ◦ Matrix protein (P17) ◦ surface glycoprotein (GP120) ◦ 2 copies of single stranded RNA ◦ Three enzymes: reverse transcriptase (RT), protease (PR), integrase (IN) By Thomas Splettstoesser (www.scistyle.com) - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=38751738 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 21 Life Cycle of HIV Summary HIV approaches the cell membrane of the human cell. The receptors on the lipid layer of the virus bind to the membrane of the cell proteins called CD4 and co-receptor CXCR-4 or CCR-5.. Once bound, the lipid rich envelope of the virus fuses with the plasma membrane of the cell, injecting the contents of the virus inside. Inside the cytoplasm, reverse transcriptase transforms the single stranded RNA molecules into the viral double stranded DNA molecules. The viral DNA then travels into the nucleus, where it is integrated into the host cells genome by using an enzyme called retroviral integrase. Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 22 Video: https://www.youtube.com/watch?v=d7LOFZaW4RM Attachment ◦ Virus: GP120 ◦ Host cell: CD4 and co-receptor CXCR-4 or CCR-5. HIV Replication Cycle Endocytosis Viral RNA and enzymes released into cytoplasm ◦ RT makes DNA copy of viral RNA ◦ RNA strand is degraded and complimentary DNA strand is added ◦ Ends of DNA strands are covalent joined à circular DNA In the nucleus ◦ Circular DNA inserted in to host cell chromosome by IN à pro-viral DNA ◦ RNA is synthesized (mRNA, viral genome RNA) Viral Messenger RNA ◦ Translation yields viral enzymes and proteins (GP41, GP120, P24, P17) Assembly and Release ◦ GP41 and GP120 inserted in to host cell membrane ◦ P24 and P17 surround viral RNA and form the core ◦ Released By Jmarchn - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=58188472 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 23 HIV Vaccine Development Using killed vaccine approach causes HIV to lose ability to bind to Tcell receptors Using live/attenuated vaccine approaches raise safety concerns Extract vaccine approach using HIV envelope proteins (especially gp120 and gp41) doesn’t work, increases rate of mutagenesis Fall 2023 | J.Memme By Gorry and others - (2007). "Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo". Retrovirology 4: 66. DOI:10.1186/1742-4690-4-66. PMID 17888184. PMC: 2075523., CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=29349195 IMMUNOLOGY | BIOT 203 24 Hear from the Scientist in charge https://youtu.be/C7yRqPpVibQ?si=aDAx-JtZxIGrRv9q Choi, E., Michalski, C. J., Choo, S. H., Kim, G. N., Banasikowska, E., Lee, S., . . . An, H.-Y. (2016). First Phase I human clinical trial of a killed whole-HIV-1 vaccine: demonstration of its safety and enhancement of anti-HIV antibody responses. Retrovirology, 13, 1-16. HIV Vaccine | SAV001 Preventative HIV vaccine Phase I Genetically modified killed whole virus ◦ Single peptide exchange ◦ Remove Gene responsible for pathogenicity ◦ Replace with gene with melittin (honey bee toxin) Educates Tc cells to recognize HIVinfected cells ◦ ◦ ◦ ◦ Tested on 33 HIV positive subjects No adverse effects Completion: September 2013 Published: Choi, et al. 2016 Phase II ◦ ◦ ◦ ◦ 600 HIV-negative subjects, high risk category North American Ability to produce anti-HIV antibodies …planned but not executed… Phase III ◦ ….. By Ricks at the German language Wikipedia, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2091885 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 25 Therapeutics Treatments that activate or suppress the immune system Possible to personalize to treat individual patient Created with BioRender.com Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 26 Progress Tracking Assessment #8 Available on Blackboard in Unit Learning Materials ◦ You are in encouraged to collaborate with your peers but must submit your own individual product. ◦ Submit via Blackboard using the assignment submission link before the end of the day. IMMUNOLOGY | BIOT 203 PTA #8: Consult available resources to classify the vaccine or therapeutic type of the listed interventions Suggested resources: • 19 Vaccine Tracker by the Department of Epidemiology and Biostatistics in the School of Population and Global Health at McGill University • https://covid19.trackvaccines.org/ • COVID-19 Vaccine &Therapeutics Tracker by BioRender • https://biorender.com/covid-vaccine-tracker • Drugs and vaccines forCOVID-19: List of authorized clinical trials by The Government of Canada • https://www.canada.ca/en/health-canada/services/drugshealth-products/covid19-industry/drugs-vaccinestreatments/list-authorized-trials.html • Contents of immunizing agents available for use in Canada: Canadian Immunization Guide by The Government of Canada • https://www.canada.ca/en/publichealth/services/publications/healthy-living/canadianimmunization-guide-part-1-key-immunizationinformation/page-15-contents-immunizing-agents-availableuse-canada.html Fall 2023 | J.Memme 27