CLS Microbiology - Spring VACCINES

Transcription

1 CLS Microbiology - Spring VACCINES 430 BC Thucydides on the the Plague of Athens (Likely the bubonic plague) Suddenly falling upon Athens, it first attacked the population in Piraeus and afterwards appeared in the upper city, when the deaths became more frequent. Fear of gods or laws of men there was none to restrain them. As for the first, they judged it to be just the same whether they worshipped them or not, as they saw all alike perishing. As for the latter, no one expected to live to be brought to trial for his offenses even the most staid and respectable citizens devoted themselves to nothing but gluttony, drunkenness and licentiousness. Yet still the ones who felt most pity for the sick and dying were those who had the plague themselves and recovered from it. They knew what it was like and at the same time felt themselves to be safe, for no one caught the disease twice, or if he did, the second attack was never fatal "Doktor Schnabel von Rom" ("Doctor Beak from Rome") engraving; Credit(s): Paul Fuerst, publisher & possible engraver (after J. Columbina); Physician attire for protection from the Bubonic plague or Black death. Rome 1656 From Accessed 30 April, 2018.

2 Immunity root from Latin: immunitas - exempt from public service immunity exempt from disease Antigen (Ag) anything that elicits immune response e.g. small parts of molecules pathogens thus have many antigens

3 Historical Perspective BC Ancient Greeks - Thucydides -1st introduced idea of immunity to infection 2. 15th century Chinese - smallpox a. Inhalation of powders from crusted lesions b. Variolation Lady Mary Montague - Wife of British ambassador to Turkey a. observed variolation and immunized her children b. brought technique to England Edward Jenner - cowpox - observations of Milkmaids - Immunized child w/ cowpox - immune to small pox - from Latin vacca for Cow 5. 19th century - Pasteur - cholera (attenuated) did not cause disease Vaccine fr. vacca - tried with anthrax - immunized sheep then a young boy protection

4 James Gillray, The Cow-Pock or the Wonderful Effects of the New Inoculation! (1802)

5 The Vaccination Act of 1898 in the UK Vaccination was Controversial. Act of 1853 made vaccination compulsory. The 1898 Act allowed parents who objected to vaccination to exempt their children. This was when the term conscientious objector was introduced.

6 The Vaccination Monster A mighty & horrible monster, with the horns of a bull, the hind of a horse, the jaws of a krakin, the teeth & claws of a tyger, the tail of a cow, all the evils of Pandora's box in his belly, plague, pestilence, leprosy, purple blotches, foetid ulcer & filthy running sores covering his body, & an atmosphere of accumulated disease, pain & death around him, has made his appearance in the world, & devores mankind (especially poor helpless infants) not by sores only, or hundreds, or thousands, but by hundreds of thousands (vide Vaccinae Vindicia: 413, 423).This monster has been named vaccination; & his progressive havoc among the human race, has been dreadful & most alarming. Yet, strange to tell, this monster has found not only a multitude of friends but worshipers, who prostrate themselves before him, & encourage his voracious appetite. Do not the men, the heroes who first dared to stand forth to arrest the progress, & stop the fatal havoc of this most dreadful & destructive monster, & at length have bravely subdued & put him to flight with all his mighty host, merit an obelisk created to their fame, with their names inscribed upon it, in indelible characters, to be held in grateful remembrance through all future generations? And are not these names moseley, rowley, birch, squirrel, lipscomb? London, 1807 Kraken mythic sea monster VACCINATION MONSTER Nothing New Under The Sun from the Vaccine Damage Prevention website, Accessed 8 Aug, 2002

7 1979 smallpox officially declared eradicated worldwidesmallpox free for ~ 3 y - vaccination ceased - last case Somalia Medline Plus - A service of the U.S National Library of Medicine & the National Institutes of health Update 8/17/2004 by: A.D.A.M. Medical Illustration Team Egyptian mummy of Pharaoh Ramses V pock-marked face (OR NOT?) Small pox outbreak c 1157 BC

8 How Vaccines work The Immune Response Innate vs. Adaptive Immunity

9 Roles of immunity Recognition/detection (Self vs. Non-self) Containment/Elimination (effector functions) Regulation no damage to host Prevent recurrence (memory)

10 The Immune system must recognize self from non-self Pathogens also have Ags unique to each species or strain Streptococcus pneumoniae vs Strep. mutans Similar bacteria share common antigens (Ag) SELF

11 Innate Immunity 1. First, Fast - Initial defense against pathogens or other antigens (Ag) 2. Fixed - present prior to infection Fixed - same in all members of species 3. Constant - during infection 4. No immunological memory - 5. Limited specificity for pathogens may clear pathogen before disease ever occurs

12 Adaptive Immunity 1. Slower (not fixed) 2. Variable/diverse - requires priming - not same in all members of species 3. Increases during infection 4. Immunologic memory 5. High Antigenic specificity small difference in Ag may mean pathogen not recognized

13 However both arms of the immune system are interdependent factors of the innate system are needed to induce adaptive immunity

14 Innate immunity- barriers physical & physiological Skin Mucosa (internal membranes) Conjunctiva, GI, Respiratory, Urogenital, Oral - washing action of mucus, cilia ph - low ph on skin, gastric, vaginal Body temp - fever Soluble components: Lysozyme Complement (C ) Cytokines

15 Innate Immunity- what happens if barriers are breached? Inflammation: Macrophages & neutrophils - major cells of innate immunity e.g. macrophage neutrophil

16 Innate Immunity - Inflammation Characterized by: Redness Swelling Pain Heat

17 Two Types of Adaptive Immunity Humoral: Antibody (Ab) mediated B-cells make Ab Ab - aka immunoglobulin (Ig) transferred by serum anti-serum Cell Mediated Immunity (CMI) - T-cells T cytotoxic cells (T C ) - kill viruses T helper cells (T H ) - help B-cells make Ab T REG cells regulate; suppress

18 Adaptive Immune Response Innate Immunity active during Lag Booster

19 Protective functions of Ab Neutralization of pathogens block attachment to tissues

20 Protective functions of Ab Neutralization of intracellular pathogens block entry

21 Protective functions of Ab Neutralization of Toxins by specific antibody

22 Cytotoxic T cells (T C ) (CD8+) can kill several infected target cells in succession.

23 Types of immunization 1. Passive Natural maternal milk, cross placenta Acquired - transfer of Ab from immune to non-immune individual (Ig injections; anti-serum) 2. Active vaccination -

24 Passive transfer of Ig Advantages: No exposure to pathogen or antigen FAST: no time to induce immunity-pooled Ig/anti-serum - bioterrorist acts or pandemics - infected people need Ab immediately. People who can t be immunized: - Pregnant woman - anti rubella Ig - immunosuppressed/physically weakened might not mount good response Disadvantages: Short lived no activation of immunity in recipient NO MEMORY serum sickness (e.g. use of horse anti-serum)

25 Passive transfer of Ig Also: Immunodeficiency Ebola

26 Active vaccination vacca fr. Ltn for cow Immunization with pathogens or parts of pathogens that don t cause disease Advantages: activate recipient immunity long term MEMORY highly specific Disadvantages: slower possible side effects

27 POISON IVY REACTION Type IV hypersensitivity Delayed Type = DTH A rash decision

28 Active vaccination Types: 1. Whole Organism a. Live attenuated - virus multiplies in host; does not cause disease b. Killed, inactivated 2. Purified macromolecules 3. Multi-valent sub-unit (liposomes) 4. DNA 5. Recombinant Vector

29 Considerations for Vaccine Design 1. Safety real/perceived 2. Protection against exposure to live pathogen 3. Long term protection MEMORY 4. What arm of immune system to activate? Antibody neutralizing CMI T H (CD4+) or T C (CD8+) 5. Delivery method 6. Public health aspects - cost - ease of delivery -compliance - stability - animal vs. human trials

30 Whole organism vaccines advantages & disadvantages Live attenuated: * more similar to natural infection better activation of all types immunity * chance of reversion to virulence * not for immunosuppressed/pregnant * may be difficult to maintain/store Killed, inactivated: * no chance reversion to virulence * safe for immunosuppressed * easier to store * immune response may be LIMITED

31 Methods for virus attenuation 1. Natural (e.g. smallpox vs. cowpox) Current small pox vaccine is Vaccinia virus - Origin?? Hybrid of smallpox & cowpox?? Possibly horse virus??

32 Methods for virus attenuation 1. Natural 2. Pass through culture

33 Methods for virus attenuation 1. Natural 2. Pass through culture 3. Genetic Engineering May be safer method to create live attenuated vaccines alter selected genes

34 Examples-whole organism vaccines Polio: Attenuated (Sabin) Tri-valent oral polio vaccine (TOPV) 3 strains Issue with reversion of one strain Inactivated (Salk) only version in US now MMR - Measles, Mumps, (live) Rubella (inact) Influenza (nasal spray) Varicella (chicken pox) Rotavirus Zostavax (Live) Yellow fever - (Live)

35 Purified Macromolecule Vaccines Protein toxoids (inactivated exotoxins) diptheria, tetanus, anthrax Purified Polysaccharides Neisseria meningitidis Conjugate vaccines (Antigen + protein carrier) Haemophilus influenza b (Hib) meningitis Recombinant DNA Hepatitis B Virus (HBsAg) Adjuvants enhance immune response

36 Cellular components (proteins, polysaccharides, other lipids) can be added to these vesicles Specific Antigen Adjuvant: Shingrix (shingles): Liposomes w/ Viral surface protein Detoxified LPS Plant derivative

37 DNA Vaccines DNA encodes protective Ag DNA of single gene + cytokine gene injected into muscle cytokine stimulates immune response Successful in mice Veterinary use Human trials-malaria, Influenza, HIV

38 Comparison of vaccine types

39 Herd Immunity in a population red = infected; blue = susceptible; yellow = immune

40 Vaccination Successes

41 Increased Measles Outbreaks in UK since 1998 Loss of herd Immunity? If US trend in Vaccine uptake mimics UK, this may least one reason for recent measles outbreaks in US From:

42 Measles risks and complications - with and without vaccination

43 Incidence of polio 1988

44 Incidence of polio 10 yrs later Can Polio be eliminated like Smallpox?? Last case US 1979, but vaccine still given Still occurs in some countries Eradication campaign ongoing

45 Current Vaccines Recommended for adults over 50 Flu vaccine yearly Td (Tetanus & diptheria) or Tdap (tetanus, diptheria, pertussis whooping cough ) (DT & DTaP - versions for young children) Shingles - healthy adults over 50 Almost 1 of 3 in U. S. will develop shingles. Increased risk w/age. Pneumococcal vaccines - adults over 65 & adults younger than 65 yrs w/chronic health conditions Travelers : Yellow fever, Malaria, Typhus, Polio booster

46 Td/DT or Tdap/DTaP National Center for Immunization and Respiratory Disease content last reviewed May 8, 2009, CURRENT LIST: Updated April 2018 accessed Jan 18, GARDASIL 9 Lyme disease vaccine removed from list no longer used in US MMR MMR (whooping cough) Tdap/DTaP OPV & IPV (inactive - currently used in US) MMR Zostavax (live), Shingrix (recombinant) NO LONGER GIVEN Td/DT or Tdap/DTaP BCG Bacillus Calmette Guerin for TB not used in US not v. effective. Foreigners who have had this may be + on a TB test BCG for TB

47 Some Fallacies about Vaccines Do vaccines cause autism? Does giving so many vaccines at a young age overload the immune system or weaken it? Do vaccines contain toxic components? Mercury & Aluminum?? If others are vaccinated I don t need a vaccination Not getting vaccinated doesn t hurt anyone else. Do vaccines cause chronic disease?

48 EXTRA SLIDES

49 Leukocyte Rolling in Zebrafish Larvae Selectins are adherence molecules involved in cell communication Cytokines include chemokines to recruit cells