Introduction to Vaccinology and Vaccines.pptx

Microbiology

1. INTRODUCTION TO VACCINOLOGY AND VACCINES ANDREW MUSYOKI [MSc, PhD (Med) Virology] Department of Microbiological Pathology, School of Medicine South African Vaccination and Immunisation Centre (SAVIC) Sefako Makgatho Health Sciences University (SMU)

2. Presentation outline The need for a defense system: Microorganisms How the human immune system works Vaccination and how vaccines work Types of vaccines 2

3. MICROORGANISMS : Bacteria and Viruses 3

4. MICROORGANISMS … 4 True pathogens overcome defenses Invade tissues Cause disease Clinical symptoms host versus invader damage directly caused by pathogen Colonize / be carried without causing illness

5. CHARACTERISTICS OF INFECTIOUS DISEASES 5

6. PATHOGENICITY 6

7. HOW THE HUMAN IMMUNE SYSTEM WORKS 7 https://www.youtube.com/watch?v=zQGOcOUBi6s

8. SUMMARY OF SPECIFIC IMMUNE RESPONSE 8

9. THE SPECIFIC IMMUNE RESPONSE 9

10. SPECIFIC IMMUNE RESPONSE … 10

11. SPECIFIC IMMUNE RESPONSE MEMORY 11

12. VACCINATION AND HOW VACCINES WORK 12

13. VACCINES AND VACCINATION 13 A vaccine is a preparation/suspension of live , weakened , killed , or fragmented microorganisms , or toxin/proteins from a pathogenic microorganism, that is given to stimulate the body's immune response against infection by the disease-causing Given by injection, by mouth or as a nasal spray. Vaccination is a simple, safe, and effective way of administering a vaccine for protection against harmful diseases before anyone encounters the disease-causing organism. • When you get a vaccine, your immune system responds/should respond. Therefore, the two key reasons to get vaccinated are to protect ourselves and to protect those around us.

14. IMMUNIZATION 14 Immunization refers to the process of both getting the vaccine which then triggers your immune system to respond and becoming immune to the disease following vaccination. When one gets a vaccine, the following happens: Body’s immune system recognizes the active vaccine component (bacterial or viral) Produces antibodies naturally to fight the virus/bacteria. Remembers the germ and how to fight it and if exposed to the germ in future, the immune system can quickly destroy it before the host becomes unwell. Adaptive immune systems are designed to remember. Rather than treating a disease after it occurs, vaccines protect us from getting sick with the disease in the first instance . Vaccination/Immunization used interchangeably in common language.

15. 20th century's most successful and cost‐ effective public health tool for preventing disease and death For people of all ages – Newborns to the elderly Timely immunisation is one of the most important ways for people to protect themselves and others from serious diseases. VACCINATION 15

16. IMPORTANCE OF VACCINATION 16

17. VACCINATION: MECHANISMS OF ACTION 17

18. IMMUNISATION SCHEDULES 18

19. Highly immunogenic , inducing a rapid, strong and specific immune response Totally effective in a single dose ; Safe: no adverse reactions or side effects Induces life-long immunity in 100% of the population Stable under non-stringent storage conditions Genetically stable (re: live vaccines) Easily administered Affordable THE “IDEAL” VACCINE 19

20. In reality, no vaccine is the “ideal” vaccine Most are highly immunogenic All vaccines have minimal side effects Most are only 80% ‐ 95% effective Oral vaccines / nasal spray vaccines are easy to administer; injected vaccines need expertise Lifelong protection usually requires boosters Most require stringent storage conditions Live vaccine s can revert to virulence (polio) Traditional vaccines are cheap; newer vaccines are very expensive “REAL” VACCINES 20

21. HOW DO VACCINES WORK? 21 https://www.nature.com/articles/s41577-020-00479-7

22. 22 TYPES OF VACCINES

23. VACCINES 23

24. A BRIEF HISTORY OF VACCINES Not to scale smallpox Smallpox vaccine (Jenner) 1796 Diphtheria antitoxin (Roux & Yersin) 1890 Polio vaccine (Salk) 1952 Measles (Enders & co) 1963 Influenza (Salk & Francis) 1983 Varicella (Takahashi) 1988 Human papillomavirus (Frazer & Zhou) 2006 1721 1885 1921 1956 1977 1985 2003 2020- 2021 Variolation Rabies Tuberculosis, Polio vaccine Haemophilus Hepatitis B Ebola rVSV- SARS-CoV- 2 introduced in (Pasteur) BCG (Calmette (Sabin) influenzae type (Blumberg) ZEBOV (Various) England to & Guérin) b (Smith & prevent Anderson) Live attenuated , inactivated , toxoid , conjugate , recombinant , viral vector , mRNA

25. Types of vaccines 7 Whole-cell inactivated Killed form of pathogen Live attenuated Weakened but live form of pathogen Viral vector Harmless virus to deliver genetic material Piece of the pathogen Subunit Small piece of the virus's genetic material RNA Toxoid Modified form of bacterial toxin Recombinant Genetically engineered antigen / proteins

26. LIVE, ATTENUATED VACCINES Virus or bacteria 'weakened' Culturing microorganisms and passaging it through non-human cells, eggs or animals Small dose administered, organism replicates and stimulates immune response Usually do not cause disease, or only mild disease Immune response very similar to natural infection Could be dangerous in immune compromised individuals Could revert to original form (e.g. oral polio vaccine) Examples: measles, mumps, rubella (MMR), varicella, rotavirus, and influenza (intranasal), typhoid vaccine (Ty21a), and Bacille Calmette- Guerin (BCG) 8 Image credit: WHO

27. INACTIVATED VACCINES Not alive, cannot replicate or cause disease Need more doses over time and protection does not last as long First dose usually only a primer for immune system Mostly produces antibody response and not cellular – requires boosters Includes whole- cell inactivated vaccines , subunit vaccines , and recombinant vaccines 9

28. WHOLE- CELL INACTIVATED VACCINES Bacteria or viruses that have been killed or inactivated Uses heat, chemicals or radiation Cannot replicate or cause disease Examples: polio, hepatitis A, rabies, pertussis whole cell vaccine 10 Image credit: WHO

29. TOXOID VACCINES Some bacteria (e.g., tetanus, diphtheria) cause disease by producing toxins The ability of the immune system to recognize and eliminate these toxins provides protection from the disease Toxoid vaccines uses inactivated toxins produced by bacteria Toxins inactivated using heat or chemicals (e.g. formaldehyde) Toxin rendered harmless, but can still stimulate immune system 11

30. SUBUNIT VACCINES Contain a portion of the bacteria or virus needed to produce a protective immune response Can be protein, polysaccharide, or a combination of polysaccharide and protein molecule (i.e., conjugate vaccine) The immune response to a pure polysaccharide vaccine is typically T- cell-independent, which means these vaccines can stimulate B- cells without the assistance of T-helper cells T- cell-independent antigens, including polysaccharide vaccines, are not consistently immunogenic in children younger than age 2 years, probably because of immaturity of the immune system Attaching ( conjugating ) the polysaccharide antigen to a protein makes it possible to prevent bacterial infections in populations where a polysaccharide vaccine is not effective or provides only temporary protection Conjugate subunit vaccines produced by chemically attaching a polysaccharide from the surface of bacteria to a protein molecule (conjugation) Example Haemophilus influenzae type b and pneumococcal conjugate vaccines Produces long- lasting protective immunity to the polysaccharide antigen 12 Image credit: WHO

31. RECOMBINANT VACCINES Produced by recombinant DNA technology Enables the combination of DNA from two or more sources Hepatitis B, human papillomavirus (HPV), and influenza (Flublok brand) vaccines are produced by inserting a segment of the respective viral gene into the gene of a yeast cell or virus The modified yeast cell or virus produces pure hepatitis B surface antigen, HPV capsid protein, or influenza hemagglutinin when it grows, which stimulates the immune system Serogroup B meningococcal vaccines are proteins and outer membrane vesicles generated by recombinant technology 13 Image credit: WHO (adapted)

32. VIRAL VECTOR A 'hollowed' out virus is used to package genetic material from the pathogen into the body The viral vector infects cells, delivers genetic material Genetic material is translated to the pathogen protein, which stimulates an immune response Examples: rVSV- ZEBOV Ebola vaccine is a recombinant vesicular stomatitis virus including a gen e from the Ebola virus SARS-CoV- 2 adenovirus vaccine is a n adenovirus containing the mRNA for coding a coronavirus spike protein 32 Image credit: WHO

33. mRNA VACCINES mRNA enveloped in a lipid (fat) sphere The body’s immune cells take up the vaccine particles and reveal the mRNA The mRNA gives the cell code to create a protein similar to a protein on the pathogen's surface The immune cell then releases that protein to other immune cells, triggering an immune response that includes antibody production and activation of specialized cells to find and kill the pathogen bearing that protein and any host cells infected Example: SARS- CoV- 2 mRNA vaccine carries the code to create a protein similar to the spike protein on the coronavirus’ surface 33 Image credit: WHO

34. Live vaccines Non- live vaccines BCG DTap and Tdap Oral polio Haemophilus influenza type b Rotavirus Inactivated polio Measles (or MMR) Hepatitis B Varicella Pneumococcal (conjugate and polysaccharide) Zoster Hepatitis A Yellow fever Influenzas Intranasal influenza Typhoid VI Oral typhoid Ty21a 34

35. 35

36. EPI-SA vaccines 36 + Birth dose HepB in HBsAg+ Tdap MR PCV10

37. Vaccine preventable diseases and Herd protection threshold 37

38. WHY ARE THERE DIFFERENT TYPES? Type of pathogen, structure, replication cycle, immune response after natural infection Vaccine safety Immunogenicity Manufacturing (ease and cost) Regulatory approval 38

39. WHICH PATHOGENS TO TARGET FOR VACCINE DEVELOPMENT Disease burden Transmission and risk factors Feasibility of control measures Scientific and technical feasibility Economic and market considerations 39

40. Vaccine components Antigen Adjuvants Preservatives Stabilizers Antibiotic 40

41. Vaccine components Antigen The part of the vaccine that triggers an immune response Specific to type of vaccine Adjuvants Substances added to some vaccines to enhance the body's immune response to the antigen Preservatives Certain vaccines, particularly those stored in multi-dose vials, contain preservatives to prevent the growth of bacteria or other contaminants Examples thiomersal, formaldehyde, phenol derivatives 41

42. Vaccine components Stabilizers Substances that help to maintain the stability and potency of the vaccine during storage and transportation e.g. maintain pH, prevent hydrolysis or aggregation Examples: magnesium chloride, magnesium sulphate, lactose-sorbitiol, sorbitol- gelatin, human serum albumin, potassium phosphate Antibiotic Trace amounts used during manufacturing process to prevent contamination Example neomycin (no penicillins, cephalosporins or sulfonamides) 42

43. Vaccine components: Adjuvants Aluminum salts Cause local reaction at the injection site, resulting in the release of cytokines, which are signaling molecules that help to activate the immune system, leads to an increase in the production of immune cells, such as T cells and B cells, which are essential for generating an immune response Example aluminum hydroxide and aluminum phosphate Liposomes Tiny spheres made of lipid molecules that can be filled with vaccine antigens Deliver antigens, stimulate immune cells (composed of lipid molecules that are similar to those found in the membranes of some pathogens), activate immune signaling pathways 43

44. Vaccine components: Adjuvants Oil-in- water emulsions Can help to stimulate both the innate and adaptive immune responses to the vaccine Pathogen- associated molecular patterns (PAMPs) Are naturally present in certain microorganisms and can stimulate the immune system Some adjuvants, such as monophosphoryl lipid A (MPL), are derived from PAMPs and can enhance the immune response to the vaccine 44

45. SUMMARY: AIM OF VACCINATION 45

46. TRADITIONAL VACCINES 46 Vaccines traditionally made from: whole killed or weakened organisms antigens that elicit an immune response Antigens are produced in a laboratory, i.e. outside of the host Purified and packaged during the manufacturing process Antigens administered as a vaccine https://microbenotes.com/vaccines-introduction-and-types/

47. NEWER VACCINE PLATFORMS 47 https://www.bloomberg.com/news/articles/2021-07-15/mrna-vaccine-access-carves-up-world-into-haves-and-have-nots mRNA vaccines Vector based vaccines

48. Foundation for rapid COVID- 19 vaccine development Coronavirus virology DNA/RNA transfection biology RSV immunology (VAERD) HIV-driven technology; clinical and research infrastructure development RSV structure- based vaccine design Prototype pathogen pandemic preparedness concepts Nucleic acid vaccine development CoV spike structure and stabilization Paramyxovirus vaccine antigen design Public- private partnerships for pandemic response Advances in human mAb discovery Advances in HIV Env structure Advances in platform manufacturing Advances in protein engineering Repeated inadequate responses to pandemic threats Development of prototype mRNA vaccines for MERS- CoV and Nipah Vaccine development for SARS-CoV- 2 40 15 20 3 8 Year(s) 1

49. CONCLUSIONS Vaccines have saved millions of lives Vaccinators must know : the different types of vaccines how vaccines are made how they prevent disease in the human body how to administer them to patients: each vaccine is unique % population vaccinated for herd immunity value of herd immunity for population protection 42 DO NOT HESITATE, VACCINATE

50. Thank you Visit: http://www.savic.ac.za/ Twitter: @SAVICinfo Facebook: SAVICinfo

51. References Bonani P, Santos JI (2011). Vaccine evolution. In: Understanding modern vaccines: perspectives in vaccinology. Elsevier. Centers for Disease Prevention and Control (2015). Vaccines and immunizations: Epidemiology and Prevention of Vaccine-Preventable Diseases. The Pink Book – 13th Edition. Available at http://www.cdc.gov/vaccines/pubs/pinkbook/index.html Plotkin S. History of vaccination. Proc Natl Acad Sci U S A. 2014;111(34):12283-7. United States Agency for International Development (2009). Immunization Essentials: A practical field guide. Available at: http://pdf.usaid.gov/pdf_docs/PNACU960.pdf De Cock KM, Simone PM, Davison V, Slutsker L (2013). The new global health. Emerg Infect Dis. 19(8):1192-7. Gundling K (2011). Your Immune system 101: Introduction to clinical immunology. University of California Television. 2011. Available at: https://www.youtube.com/watch?v=_oI0jVN4TTI Leo O, Cunningham A, Stern PL. Vaccine immunology. In: Understanding modern vaccines: perspectives in vaccinology. 2011; Elsevier. Kumar V, Abbas AK, Fausto N, Mitchell RN. Chapter 5: Diseases of the immune system. In: Robbins Basic Pathology, 8th edition. Saunders Elsevier; 2007. p107-172 NIAID (2014). Overview of the immune system. Available at https://www.niaid.nih.gov/research/immune- system-overview NIAID (2014). Features of an immune response. Available at https://www.niaid.nih.gov/research/immune-response-features NIAID (2014). Immune cells. Available at https://www.niaid.nih.gov/research/immune-cells NIAID (2014). Immune tolerance. Available at https://www.niaid.nih.gov/research/immune-tolerance