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VACCINES, LECTURE Flashcards

1
Q

BEFORE THE AGE OF VACCINES, HOW MANY CHILDREN WERE DYING FROM INFECTIOUS DISEASES?

A

CCA 1/3

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2
Q

THE ‘MOTHER OF PANDEMICS’ IS CONSIDERED TO BE?

A

1918 SPANISH INFLUENZA

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3
Q

A DROP IN LIFE EXPECTANCY IN ENGLAND AND WALES AROUND 1725 IS BELIEVED TO BE A RESUKT OF OUTBREAK OF WHICH ILLNESS?

A

SMALL POX

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4
Q

HISTORY OF BASIS OF VACCINATION:

A
  • IN 1976 AN ENGLISH DOCTOR EDWARD JENNER NOTICED THAT MILKMAIDS WHO HAVE BEEN INFECTED WITH COWPOX WERE PROTECTED FROM SMALLPOX
  • JENNER WAS AWARE OF VARIOLATION (INSERTING SMALLPOX SCABS UNDER THE SKIN TO PROVIDE IMMUNITY) AND THEN GUESSED THAT EXPOSURE TO COWPOX COULD BE USED TO PROTECT AGAINST SMALLPOX
  • JENNER TESTED THE THEORY BY TAKING MATERIAL FROM A COWPOX SORE ON A MILKMAID’S HAND AND INCOLUTING IT INTO THE ARM OF A 9 YEAR OLD BOY
  • HE LATER EXPOSED THE BOY TO VARIOLA VIRUS BUT THE BOY NEVER GOT SMALLPOX
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5
Q

WHAT IS VARIOLATION?

A

INSERTING SMALLPOX SCABS UNDER THE SKIN TO PROVIDE IMMUNITY

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6
Q

WHO USED THE TERM VACCINE AND WHEN? ORIGIN OF THE WORD?

A

1897: LOUIS PASTEUR (DEVELOPED RABIE VACCINE)

ORIGINATED FROM ‘VACCA’, WHICH IS LATIN FOR COW (IN HONOR OF EDWARD JENNER’S WORK)

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7
Q

WHEN DID WHO DECLARE SMALLPOX ERADIACTED?

A

1980

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8
Q

WHAT IS THE ONLY PATHOGEN IN HUMAN HISTORY THAT WAS EARDIACTED THROUGH VACCINATION?

A

SMALLPOX

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9
Q

WHERE/WHEN WAS THE LAST CASE OF SMALLPOX?

A

SOMALIA, OCTOBER 12, 1977

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10
Q

HAS POLIO BEEN ERADICATED?

A

NO, BUT IT HAS BEEN WEAKENED BY THE VACCINE

- STILL PRESENT IN PAKISATN AND AFGHANISTAN

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11
Q

WHAT IS A VACCINE?

A
  • VACCINES MIMIC A PATHOGEN AND STIMULATE A PROTECTIVE IMMUNE RESPONSE
  • THEY STIMULATE IMMUNE MEMORY, WHICH ALLOWS THE BODY TO BE PREPARED TO FIGHT OFF INFECTION IN THE FUTURE
  • IMMUNE SYSTEM FORM OF MEMORY ARE SPEICAL TYPES OF LYMPHOCYTES CALLED MEMORY B ANT T CELLS
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12
Q

WHICH CELLS PARTICIPATE IN THE IMMUNE MEMORY CREATED BY VACCINATION? WHERE DO THESE CELLS RESIDE?

A

MEMORY B AND T CELLS (SPECIAL TYPES OF LYMPHOCYTES)

RESIDE IN GERMINAL CENTRES, LYMPHATIC SYSTEM INCLUDING THE SPLEEN AND THE BONE MARROW

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13
Q

WHAT CAN VACCINES BE USED AGAINST?

A

VIRUSES (BEST/MOST EFFECTIVE APPLICATION), BACTERIA AND CANCER

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14
Q

PROPHYLACTICS VS THERAPEUTICS?

A

PROPHYLACTICS: PREVENTION FOCUSED: E.G. VACCINE - PREPARE THE IMMUNE SYSTEM TO DEFEND THE BODY AGAINST INFECTION, BETA BLOCKERS - HEART ATTACK PREVENTION, BIRTH CONTROL, TENOFOVIR/EMTRICITABINE (HIV PRE EXPOSURE PROPHYLAXISIS)

THERAPEUTICS: INTERVENTIONS WHICH ARE UNDERTAKEN DURING INFECTION OR ILLNESS TO HELP THE BODY FIGHT DISEASE (E.G. MONOCLONAL ANTIBODIES, IMMUNOSUPPRESSANTS, GENE THERAPY)

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15
Q

WHAT DOES THE HERD IMMUNITY TRESHOLD DEPEND ON?

A

IT IS PATHOGEN SPECIFIC

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16
Q

HERD IMMUNITY TRESHOLD FOR SMALLPOX?

A

80-85%

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17
Q

HERD IMMUNITY TRESHOLD FOR MEASLES?

A

93-95%

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18
Q

WHICH VACCINES ARE 100% EFFECTIVE?

A

NONE

E.G. WHEN 80% OF POPULATION IS VACCINATED AGAINST MEASLES, 76% ARE ACTUALLY IMMUNE

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19
Q

R0 FOR SARS COV 2?

A

2-3

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20
Q

R0 DEFINITION

A

AVERAGE NUMBER OF CASES OF AN INFECTIOUS DISEASE ARISING BY TRANSMISSION FROM A SINGLE INFECTED INDIVIDUAL, IN A POPULATION THAT HAS NOT PREVIOUSLY ENCOUNTERED THE DISEASE

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21
Q

HOW CAN HERD IMMUNITY THRESHOLD BE CALCULATED?

A

1-(1/R0)

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22
Q

BASED ON THE FORMULA FOR HERD IMMUNITY TRESHOLD, WHAT DOES THAT NUMBER EQUAL TO FOR COVID? WHY IS IT LIKELY THAT THE TRUE PERCENTAGE IS HIGHER?

A

50-70%
REAL TRESHOLD FOR HERD IMMUNITY IS LIKELY HIGHER AS THE FORMULA 1-(1/R0) DOESN’T ACCOUNT REDUCED IMMUNITY THROUGH VIRAL MUTATION OR A DECREASED IMMUNE RESPONSE

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23
Q

MAIN COMPONENTS OF A VACCINE?

A

THE 2 MAIN COMPONENTS;
1) VECTOR OR PLATFORM (A DELIVERY SYSTEM, USED TO INDUCE THE IMMUNE RESPNSE AGAINST THE ANTIGEN TARGET)
2) ANTIGEN OR VACCINE TARGET (PART OF A VIRUS OR BACTERIA THAT PRODUCES AN IMMUNE RESPONSE)
+ SOMETIMES A THIRD ONE ADDED: AN ADJUVANT (A SUBSTANCE THAT HELPS MIMIC THE INFLAMMATORY EFFECT OF INFECTION, PRODUCING A BETTER IMMUNE RESPONSE

24
Q

INFLUENZA GENOME?

A
  • NEGATIVE STRAND RNA
  • GENOME COMPOSED OF 8 SEGMENTS
  • THE 8 SEGMENTS OF RNA ENCODE 13 PROTEINS
25
Q

WHAT IS THE MAJOR SURFACE ANTIGEN IN INFLUENZA?

A

HAEMAGGLUTININ (HA)

26
Q

HOW MANY MONOMERS DOES HAEMAGGLUTININ (MAJOR SURFACE ANTIGEN IN INFLUNZA) CONSIST OF?

A

3 (A TRIMERIC PROTEIN: EACH MONOMER CONSISTS OF A HEAD DOMAN AND A STEM DOMAIN)

27
Q

INFLUENZA ATTACHMENT AND ENTRY VIA HA (HAEMAGGLUTININ)?

A

HA BINDS TO SIALIC ACID AND INITIATES MEMBRANE FUSION, LEADING TO ENDOCYTOSIS

28
Q

WHICH TYPES OF INFLUENZA VIRUS CIRCULATE IN HUMANS?

A

A AND B

29
Q

HOW MANY DEATHS AND HOW MANY SEVERE CASES DOES INFLUENZA CAUSE EACH YEAR WORLDWIDE?

A

200,000-600,000 DEATHS

1-4 MILLION SEVERE CASES

30
Q

INFLUENZA VACCINE TYPES?

A
  • WHOLE INACTIVATED VIRUS
  • SPLIT INACTIVATED VIRUS
  • LIVE ATTENUATED INFLUENZA VIRUS (LAIV)
31
Q

TRIVALENT AND QUADRIVALENT INFLUENZA VACCINES (TIV/QIV) CONSIST OF?

A
  • ONE STRAIN OF H1N1 INFLUENZA A
  • ONE STRAIN OF H3N2 INFLUENZA A
  • ONE OR TWO STRAINS OF INFLUENZA B (VICOTRIA AND/OR YAMAGATA LINEAGE)
32
Q

INFLUENZA VACCINE SHORTCOMINGS/LIMITTIONS?

A
  • THE CURRENT VACCINES INDUCE ANTIBODIES WHICH TARGET REGIONS OF THE VIRUS THAT ARE HIGHLY VARIABLE
  • TIV/QIV NEED TO BE ADMINISTERED EACH YEAR AND REFORMULATED ON AVVERAGE EVERY 3 YEARS
  • THEY TYPICALLY PROVIDE PROTECTION TO ONLY 33% OF INDIVIDUALS WHO RECEIVE IT
  • AS THE CURRECT VACCINES NEED TO BE FORMULATED 6 MONTHS PRIOR TO INFLUENZA SEASON, THE STRAINS THAT ARE SUBSEQUENTLY PREVALENT IN THE ACTUAL FLU SEASON DO NOT ALWAYS MATCH THE STRAINS USED IN THE VACCINE, LEADING TO EVEN FURTHER REDUCTIONS IN PROTECTION
33
Q

TIV/QIV FOR INFLUENZA NEED TO BE REFORMULATED HOW OFTEN?

A

ON AVERAGE EVERY 3 YEARS

34
Q

% OF PEOPLE ACTALLY PROTECTED AFTER A FLU VACCINE?

A

33%

35
Q

WHICH STEPS NEED TO BE TAKEN IN PRODUCTION OF INFLUENZA VACCINE?

A
  • IDENTIFICATION OF NEW VIRUS
  • PREPARATION OF THE VACCINE STRAIN
  • VERIFICATION OF VACCINE STRAIN
  • PREPARATION OF REAGENTS TO TEST VACCINE
  • OPTIMISATION OF VIRUS GROWTH CONDITIONS
  • BULK MANUFACTURE OF VACCINE
  • QUALITY CONTROL
  • VACCINE FILLING AND RELEASE
  • CLINICAL TRIAL
36
Q

WHAT SHOULD A UNIVERSL FLU VACCINATED BE ABLE TO DO? (WHO AND OTHER ORGANISATIONS PUSHING FOR PRODUCTION OF A MORE APPROPRIATE VACCINE)

A
  • BE AT LEAST 75% EFFECTIVE
  • PROTECT AGAINST GROUP I AND GROUP II INFLUENZA A VIRUSES
  • HAVE DURABLE PROTECTIO THAT LASTS AT LEAST 1 YEAR
  • BE SUITABLE FOR ALL AGE GROUPS
    + AS CHEAP AS POSSIBLE
37
Q

NEW APPROACHES TO INFLUENZA VACCINE?

A

1) TARGETING CONSERVED REGIONS OF HA
2) TARGETING INTERNAL PROTEINS WITHN THE VIRUS (USES T CELL IMMUNITY)
3) USING EPIDEMIOLOGY AND EVOLUTIONARY THEORY TO DESIGN VACCINE TARGETS
- –> THIS WORK CONSISTS OF PRECLINICAL!!! STUDIES WHERE VACCINES ARE TESTED IN MICE

38
Q

EXPLAIN THE THEORY BEHIND POSSIBLY CREATING A FLU VACCINE BY TARGETING CONSERVED REGIONS OF HA?

A
  • THIS CONCEPT WOULD INVOLVE AVOIDING THE VARIATION SEEN IN THE ‘HEAD DOMAIN’ OF THE HA BY TARGETING MORE CONSERVED REGION OF THE STEM
  • THIS CAN BE ACHIEVED BY CREATING A STABILISED VERSION OF THE STEM, OR BY REPLACING THE HEAD DOMAIN OF THE HA WITH A DIVERSE RANGE OF HA HEADS
  • THE STEM OF THE HA IS HIDDEN FROM THE IMMUNE RESPONSE UNDE THE BULBOUS HA HEAD –> A PRIME-BOOST STRATEGY IS THEREFORE USED TO ‘FOCUS’ THE IMMUNE RESPONSE ONTO THE STEM DOMAIN BY CREATING B AND T CELL MEMORY
  • BY VARYING THE VACCINE CONSTRUCTS, THE IMMUNE SYSTEM IS FCUSED ON REGIONS OF THE VACCINE IT HAS SEEN BEFORE AND THIS IS KNOWN AS HETEROLOGOUS PRIME-BOOST VACCINATION REGIMEN* multiple immunizations (i.e. “prime-boost” —-> THIS MEANS THAT WE COULD GIVE VACCINE IN DOSES AND IN EVERY DOSE MAKE THE HEAD DIFFERENT BUT THE STEM OF HA THE SAME AND THIS WOULD LEAD TO IMMUNE SYSTEM INCREASINGLY FOCUSING ON THE FAMILIAR COMPONENT, I.E. THE HEAD IN THIS CASE
  • THIS METHOD PROVIDES PROTECTIN IN MICE
39
Q

WHAT IS THE HETEROLOGOUS PRIME BOOST VACCINATION REGIMEN?

A

BY VARYING THE VACCINE CONSTRUCTS, THE IMMUNE SYSTEM IS FCUSED ON REGIONS OF THE VACCINE IT HAS SEEN BEFORE AND THIS IS KNOWN AS HETEROLOGOUS PRIME-BOOST VACCINATION REGIMEN multiple immunizations (i.e. “prime-boost”

40
Q

IS THE STEM OR HEAD COMPONENT OF THE FLU HA PROTEIN MORE VARIABLE?

A

HEAD

41
Q

DISADVANTAGES AND ADVANTAGES OF POTENTIALLY DEVELOPING A FLU VACCINE WHICH WOULD TARGET CONSERVED REGIONS OF THE HA PROTEIN?

A

ADV:

  • ONE VACCINE CAN TARGET AN ENTIRE SUBTYPE OR LINEAGE (I.E. H1 OR H3)
  • TYPICAL PRODUCTION METHODS CAN BE USED TO MAKE THE VACCINE

DISADV:

  • AN IMMUNORECESSIVE PART OF THE PROTEIN IS BEING TARGETED SO IT IS HARDER TO PRODUCE A PROTECTIVE IMMUNE RESPONSE
  • THE STEM IS MORE HIDDEN FROM THE IMMUNE RESPONSE AND HAS FEWER FUNCTIONALLY IMPORTANT REGIONS SO IT IS LESS PROTECTIVE THAN TARGETING THE HEAD
42
Q

LINEAGE?

A

An evolutionary lineage is a temporal series of populations, organisms, cells, or genes connected by a continuous line of descent from ancestor to descendant. Lineages are subsets of the evolutionary tree of life. Lineages are often determined by the techniques of molecular systematics.

43
Q

EXPLAIN THE THEORY BEHIND THE STRATEGY OF TARGETING CONSERVED INTERNAL PROTEINS FOR DEVELOPMENT OF A NEW UNIVERSAL FLU VACCINE?

A

INTERNAL PROTEINS TARGETED: NUCLEOCAPSID (NP) AND MATRIX PROTEIN-1 (M1)
- APPROACH TRIES TO AVOID TARGETING THE MORE VARIABLE HEAD DOMAIN OF HA
- INDUCES IMMUNITY TO INTERNAL PROTEINS BY INDUCING CD8+ T CELL MEDIATED RESPONSE AGAINST THEM
- FOR THIS TO BE ACHIEVED, VECTOR CALLED AN ADENOVIRUS WHICH INFECTS CELLS AND EXPRESSES NP AND M1 WITHIN THEM NEEDS TO BE USED
- THESE PROTEINS ARE DIGESTED AND DISPLAYED ON HLA PROTEINS ON THE SURFACE OF CELLS, WHICH IN TURN INDUCE T-CELL MEMORY RESPONSES
VECTORS USED: ADENOVIRUS FROM CHIMPS (ChadOx) AND MODIFIED VACCINIA ANKARA (MVA: smallpox vaccine)
- when testing in mice: prime-boost vaccination strategy followed by influenza challenge

44
Q

ADVANTAGES AND DISADVANTAGES OF THE POSSIBEL FLU VACCINE STRATEGY TARGETING CONSERVED INTERNAL PROTEINS OF A VIRUS?

A

ADV:
- A SINGLE VACCINE CAN BE USED TO TARGET THE WHOLE OF VIRUS TYPE (I.E. INFLUENZA A OR INFLUNZA B, NUT JUST A SINGLE SUBTYPE)

DISADV:

  • NEW PRODUCTION METHODS ARE REQUIRED (ADENOVIRUS VACCINES AND POTENIALLY MVA) –> THIS IS NOW LES OF A CONCERN BECAUSE OF THE METHODS USED IN ASTRAZENECA SARS COV 2 VACCINE)
  • T CELL RESPONSES THAT ARE THE BASIS OF THIS METHOD ARE NOT AS PROTECTIVE AS IMMUNE RESPONSES, ESP ANTIBODIES, WHICH TARGET THE HEAD DOMAIN AND PREVENTING VIRAL ATTACHMENT TO TARGT CELLS
45
Q

OVERVIEW OF THE STRATEGY TARGETING RSTRICTED IMMUNOGENIC EPITOPES FOR DEVELOPMENT OF NEW UNIVERSAL FLU VACCINE?

A
  • TARGETS HIGHLY IMMUNOGENIC REGIONS IN THE HEAD DOMAIN OF HA, WHICH ARE NOT COMPLETELY CONSERVED BUT APPEAR TO BE RESTRICTED IN THEIR VARIATION (THERE ARE SITES WITHIN THE HEAD WHICH ARE MORE CONSERVED!!)
  • IN TURN, THESE REGIONS APPEAR TO RESTRICT THE EVOLUTION OF FLU
    3 STEPS:
  • PREDICT EPITOPES ON THE SURFCE OF HA BASED ON ANTIBODY BINDING SITE AREA
  • CALCULATE THE AMINO ACID POSITIONS IN THE PREICTED ANTIBODY BINDING SITES
  • CALCULATE THE NUMBER OF COMBINTIONS AT EACH PREDICTED ANTIBODY BINDING SITE
46
Q

ADVANTAGES AND DISADVANTAGES OF TARGETING THE RESTRICTED IMMUNOGENIC EPITOPES AS A STRATEGY FOR NEW FLU VACCINE?

A

ADV:

  • TARGETING HIGHLY IMMUNOGENIC AND PROTECTIVE REGIONS OF INFLUENZA
  • CAN BE INCORPORATED INTO THE CURRENT FLU VACCINE

DISADV:
- COMPLICATED TO ACHIEVE; NEED TO KNOW HOW THE VIRUS EVOLVES

47
Q

SARS COV 2 STRUCTURE:

A
  • POSITIVE SINGLE STRANDED VIRUS
  • MAJOR ANTIGEN IS THE SPIKE PROTEIN WHICH IS A TRIMER
  • GENOME ENCODES 16 PROTEINS
48
Q

WHICH RECEPTOR DOES SARS COV 2 TO BIND TO? WHAT OCCURS AFTER BINDING?

A

ACE 2

- BINDING TRIGGERS ENDOCYTOSIS AND THEN FUSION AND COATING

49
Q

POLIO, SMALLPOX, FLU…. WHICH VIRUSES ARE HIGHLY VARIABLE?

A

JUST INFLUENZA

50
Q

HOW MANY MUTATIONS DOES OMICRON HAVE?

A

32

51
Q

DESCRIBE THE TRADITIONAL APPROACHES USED IN SEARHING FOR SARS COV 2 VACCINE?

A
  • INACTIVATED VACCINES (VIRUS GROW IN CELL CULTURE AND THEN CHEMICALLY INACTIVATED: ESTABLISHED AND SAFE BUT NOT VERY PROTECTIVE, CAN BE HARD TO PRODUCE, EXPENSIVE)
  • LIVE ATTENUATED VIRUSES (MADE OF GEETICALLY WEAKENED VERSIONS OF SARS COV 2 THAT S GROWN IN CULTURE: ESTABLISHED BUT NOT VERY PROTECTIVE OR SAFE = COMPARATIVELY EXPENSIVE)
  • RECOMBINANT PROTEIN VACCINES (CHEAP AND SAFE, BUT SOMETIMES NOT IMMUNOGENIC AND CAN BE HARD TO PRODUCE)
  • REPLICATION INCOMPETENT VACCINES (CANNOT PROPAGATE IN THE CELLS OF THE VACCINATED INDIVIDUAL BUT EXPRESS THE SPIKE PROTEIN WITHIN THEM: ESTABLISHED AND SAFE BUT RELATIVELY EXPENSIVE)
52
Q

DESCRIBE THE NEW APPROACHES THAT HAVE BEEN ADOPTED IN THE SEARCH FOR COVID VACCINE?

A
  • REPLICATION COMPETENT VACCINS (IMMUNOGENIC BUT HARD TO PRODUCE AND EXPENSIVE)
  • INACTIVATED VIRUS VECTOR VACCINES (CARRY COPIES OF THE SPIKE PROTEIN ON THEIR SURFACE BUT HAVE BEEN CHEMICALLY INACTIVATED: IMMUNOGENIC BUT DIFFICULT TO PRODUCE AND EXPENSIVE)
  • DN VACCINES (QUICK AND CHEAP BUT UNPROVEN IN HUMANS)
  • RNA VACCINES (QUICK, CHEAP, IMMUNOGENIC) —> BioNTech and Moderna
53
Q

VACCINE DEVELOPMENT TIMELINE BEFORE AND DURING COVID? REASONS?

A

TRADITIONAL DEVELOPMENT TOOK 15+ YEARS

COVID VACCINE 10 MONTHS TO 1.5 YEARS —> REQUIRED PAPERWORK REDUCED + MONEY INFLUX!!!!!

54
Q

DEVELOPMENT OF WHICH VACCINE VECTOR HAS BEEN PARTICULARLY SPED UP DUE TO COVID PANDEMIC?

A

mRNA

55
Q

GUILLAIN-BARRE SYNDROME - ASSOCIATION WITH VACCINATION?

A
  • AN AUTOIMMUNE DISEASE WHERE THE BODY’S NERVES ARE ATTACKED BY THE IMMUNE SYSTEM
  • MOTOR SYMPTOMS, SENSORY SYMPTOMS, DECREASED CONSCIOUSNESS, ATAXIA
  • OCCURS IN 1-2 PER 100,000 INDIVIDUALS VACCINATED EACH YEAR –> 7.5% OF THOSE PEOPLE WILL DIE
  • TENDS TO BE ASSOCIATED WITH GI INFECTION (CAMPYLOBACTER JEJUNI) COINCIDING WITH VACCINATION IN SOME ISTANCES
56
Q

CUTTER LABS INCIDENT?

A

1955: CUTTER LABS PRODUCED AN INACTIVATED POLIO VACCINE BUT FAILED TO INACTIVATE THE VACCINE FULLY
- 120 000 DOSES GIVEN, 40 000 CHILDREN DEVELOPED POLIO, 56 WERE PARALYSED, 5 DIED

57
Q

ANTIBODY DEPENDENT ENHANCEMENT?

A

Antibody-dependent enhancement (ADE) is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells, followed by its replication
(E.G. COMPANY SANOFI PRODUCD A VACCINE AGAINST DENGUE MATCHING 3/4 SEROTYPES OF DENGUE, WHICH LEAD TO ENHANCEMENT OF DISEASE)

INF (40 decks)

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