Lecture #10 - Vaccines

Question 1

Vaccines

Answer 1

• Vaccines work to prime the immune system by stimulating primary immune responses
- Should not cause disease
- Desired goal is the production of memory cells that can be activated if ever the pathogenic material is encountered at a later time
- Vaccines are especially beneficial to protect against viral infections
– Virus cannot be eliminated with chemotherapy (antibiotics & antimicrobial drugs)
- viral infection have v. few antivirals that exist & the one’s that do exist are typically reserved for Herpes infection, HIV, influenza
- if end up with infection & if immune system can’t clear it, it either stays or kills you, therefore vaccinating can help
*- vaccines are esp. effective for vial infections
— Prevention makes the most sense
• Some vaccines have greater risk factors than others
- some have allergic response, adverse response, or fine & protective

Question 2

Vaccines are called

Answer 2

Artificial Active Immunity

Question 3

Vaccines categories include:

Answer 3

• Live attenuated vaccines
• Whole agent inactivated vaccines
• Subunit vaccines
• Toxoid vaccines
• Viral Vector vaccines
• mRNA vaccines

Question 4

Live attenuated vaccines offer…

Answer 4

only one on list that offers BOTH cell mediated & antibody mediated immunity

Question 5

Whole agent inactivated vaccines, Subunit vaccines & Toxoid vaccines can only give

Answer 5

antibody mediated response

Question 6

Live attenuated vaccines:

Answer 6

• Consists of pathogen that has been weakened

• Usually accomplished by introducing a key mutation
• Still maintains many of the properties of the wild-type pathogen (naturally occurring/disease causing form)
  Ex) virus can still adsorb and penetrate but CANNOT REPLICATE
• Stimulates BOTH antibody and cell mediated immunity
• micking real deal if you ever see infection in natural setting
• give strongest, most beneficial immune response
• Can spontaneously mutate back to the wild-type (*reversion to the wild-type)
• • Potential to cause disease that you are trying to prevent

Question 7

Live attenuated vaccine process/idea

Answer 7

• introduce virus to human’s cells in an artificial setting in a flask, let virus have its way with those cells by replicating & through multiple passages (split cells & put in diff flasks - dilute, give them fresh media, a flask & viruses in them)
• allow virus to go through multiple replication rounds & as it goes through that, the outcome is that the virus is acquiring mutations over time
• DON’T want mutations to be such that virus doesn’t have antigenic specificity that it once did - imp. that it has enough similarity to its initial form, that it’s gonna mount same immune response, otherwise vaccine is useless
• • but want there to be mutation such that this virus is gonna be deficit in terms of its ability to cause disease (b/c would cause paralytic polio for ex - dangerous)
• idea: strike a balance
• enough mutation - that it’s NOT able to cause disease
• but not so much mutation - that it’s gonna be able to not mount an effective memory response if you ever see it

Question 8

Describe how the Live attenuated vaccine stimulates BOTH antibody and cell mediated immunity

Answer 8

antibody mediated immunity - against EXOgenous antigen
- inject vaccine & its particles float in ECF - it’s exogenous, you need antibodies made to neutralize that

cell mediated immunity - against ENDOgenous antigen
- b/c virus has ability to go inside cell & create an abnormal cell that’s gonna be destructed by immune system

Question 9

Live attenuated vaccines

Examples include:

Answer 9

Sabin vaccine against Poliovirus,

Rotavirus vaccine,

MMRV vaccine (Measles, Mumps, Rubella, Varicella),

some Rabies vaccines,

vaccine against Mycobacterium tuberculosis

Question 10

Sabin vaccine against Poliovirus

Answer 10

(in case of reversion, can cause perilytic polio & infected person is shedding the infectious form of virus which can now spread to other hosts)

• (FECAL ORAL virus - means normally be getting IgA, but fact this is injected; 1st always IgM & next is IgG (therefore most effective)
• • INJECTED IgM 1st –> IgG

Live attenuated vaccine

Question 11

Rotavirus vaccine

Answer 11

(drank by babies to prime immune system along same port of passage that normal viral infection will prime)

• live attenuated & *also give the natural route –> IgM 1st –> IgA (the best)
• get antibody mediated & cell mediated immunity

Live attenuated vaccine

Question 12

MMRV vaccine (Measles, Mumps, Rubella, Varicella),

Answer 12

Live attenuated vaccine

Question 13

Some Rabies vaccines

Answer 13

• caused by Rhabdovirus & not all vaccine avail is live attenuated, some are inactive

Live attenuated vaccine

Question 14

Vaccine against Mycobacterium tuberculosis

Answer 14

• BCG
• not greatest, poor effectiveness, given only to children

Live attenuated vaccine

Question 15

What is the type of antibody that we always begin by producing against an infection?

Answer 15

IgM

Question 16

What type of antibody do we switch to if you’re getting a mucosal infection (RT, DT, repro T, etc.), what would be mucosal form of antibody?

Answer 16

IgA

Question 17

Flu mist vaccine

Answer 17

Live attenuated vaccine

sprayed intranasally IgM –> IgG

Question 18

Would you wanna give Flu mist vaccine (live attenuated, sprayed intranasally IgM –> IgG) to someone’s who’s pregnant, AIDS patient, transplant patient, etc.?

Answer 18

NO - b/c they are immunosuppressed
- don’t give live attenuated vaccines to these risks groups b/c they’re in a disadvantageous or vulnerable state (dangerous)

Question 19

Whole agent inactivated vaccines:

Answer 19

• INCLUDE INACTIVATED VIRUS

• INCAPABLE of adsorption or penetration –> *remains EXOgenous antigen (only gives antibody mediated immunity ONLY)
• NO RISK of causing disease

• ONLY stimulates antibody mediated immunity

(like you gutted infectious material, same way you removed vital organs & so infectious ability is gone, but external antigens have not changed (recognition events are still okay)

Question 20

Whole agent inactivated vaccines

Examples include:

Answer 20

Hepatitis B vaccination,

the flu shot, Rabies vaccine used in humans,

Salk vaccine for Poliovirus

Question 21

Hepatitis B vaccination

Answer 21

Whole agent inactivated vaccines

3 dose regimen - meaning weaker response; need to dose it

1st prime, 2nd people have protective titer (higher Ab levels/but not all), 3rd ~ everybody has protective Ab (higher Ab levels)

Question 22

The flu shot

Answer 22

Whole agent inactivated vaccine

injected: IgM –> IgG

• not greatest for respir. infection
• & only exogenous antigen, therefore not getting cell mediated immunity

Question 23

Rabies vaccine used in humans

Answer 23

Whole agent inactivated vaccine

vet’s

Question 24

Salk vaccine for Poliovirus

Answer 24

Whole agent inactivated vaccine

• 0 risk of reversion to the wild type
• no one will get perilytic polio b/c received it
• some will get perilytic polio when receive Sabin vaccine (low risk factors)

Question 25

Subunit vaccines:

Answer 25

- take recognizable traits out - but still get pieces if ever encounter real deal in the envir. • Include PURIFIED PROTEINS (antigen) taken from pathogenic bacteria and virus • Does NOT contain ANY infectious material - VERY SAFE • ONLY stimulates antibody mediated immunity - b/c EXOgenous antigen (only outside cell) - therefore, Ab mediated immunity only * Cost is inhibitory - don't put every viral antigen in each vaccine - do affinity asate, immunogenicity asate, binding asate - FIND STRONGEST IMMUNOGENICITY (get attention of immune system quickest & produce the strongest antibody binding - best affinity) to include

Question 26

Subunit vaccines Examples include:

Answer 26

Hepatitis A vaccination, Human Papilloma Virus Vaccine, pneumoshot (contains purified capsule from Streptococcus pneumoniae), meningococcal vaccine (contains purified capsule from Neisseria meningitidis)

Question 27

Hepatitis A vaccination

Answer 27

Subunit vaccine

Question 28

Human Papilloma Virus Vaccine

Answer 28

Subunit vaccine - indirect protection against cervical cancer (HPV)

Question 29

Pneumoshot

Answer 29

basically bacterial vaccine b/c capsule will be outermost layer (contains purified capsule from Streptococcus pneumoniae) Subunit vaccine

Question 30

Meningococcal vaccine

Answer 30

(contains purified capsule from Neisseria meningitidis) Subunit vaccine

Question 31

Toxoid Vaccines:

Answer 31

* Consist of BACTERIAL TOXINS that have been MODIFIED * Maintain the SAME ANTIGENIC PROPERTIES of the actual toxin - (think: stand in, in a movie - can't act same way but looks same) - Toxoid is INCAPABLE of causing the same EFFECTS as the toxin - - VERY SAFE • ONLY stimulate antibody mediated immunity • Often provide SHORT-LIVED protection - BOOSTER SHOTS NEEDED (*every 10-15 years)

Question 32

Toxoid Vaccines Toxoid ex

Answer 32

Corynbacterium diptheriae produces dipheria toxin (causes respir. toxicity; destroys respir. cells) - suffocate ppl to death by forming pseudomem's considered EXOTOXIN (EXOgenous antigen) - secreted outside & can cause disease diptheria toxoid - (looks like real deal to be able to provide immune response that'll be protective, however not same b/c can't actually give you disease) - no toxic effects, but will provide memory response - therefore maintains same antigenic properties as actual toxoid

Question 33

Toxoid Vaccines Examples include:

Answer 33

DTaP vaccine against diptheria toxin, tetanus toxin, and pertussis toxin

Question 34

DTaP vaccine against diptheria toxin

Answer 34

Toxoid Vaccine DPT before (cellular pertussis - caused adverse effects/undesired symptoms; saw decreased vaccine uptake, but more effective) now DTaP - acellular - alleviated probs but vaccine is less effective, more ppl get

Question 35

If described as exotoxin, do you figure in real life will you get a cell med. immune response against real deal?

Answer 35

NO - b/c. toxin stays outside (exogenous antigen) | - not a deficiency, just way it is - normally wouldn't see cell med. immunity & with vaccine don't either

Question 36

If you've been vaxxed with DTaP or DPT, you still get infected, but...

Answer 36

when bacterium starts pumping out toxin, your memory response activate & don't get signs & symptoms of toxin disease

Question 37

Tetanus toxin

Answer 37

Toxoid Vaccines

Question 38

Pertussis toxin

Answer 38

Toxoid Vaccines

Question 39

Conjugated vaccines:

Answer 39

- to deal with poor immunity that children normally have, you'll give a conjugated vaccine for some things • Consists of antigen that have been conjugated together - Increases the overall size of the antigen - Addresses limitations of naïve (ill-experienced) adaptive immune system in children - Increased immunogenicity= better protection BASICALLY 2 things together so bigger, so immune system is more likely to recognize, detect & initiate response & proceed as more

Question 40

Polysaccharide vaccine against capsule of Haemophilus influenzae conjugated to protein

Answer 40

Conjugated vaccines could take diptheria toxoid & conjugate with capsular polysaccharide against H. influenza - then inject it - bigger (easier for immune system to see & recognize) - produce antibodies both (b/c see all of it as foreign antigen) - - protective response against everything

Question 41

Viral Vector Vaccine

Answer 41

ex) Johnson & Johnson SARS-COV-2 vaccine ex) Adenovirus (genome) gene for SARS-COV-2 spike protein inject to vaccine recipient 1. Virus comes in & starts producing spike protein using host cell machinery 2. Spike protein secreted = EXOgenous antigen --> Ab production (against it) 3. Internally take MHC I & some antigen & traffic it into surface - MHC I & spike antigen will elicit an ENDOgenous antigen (cell med. immune response --> memory; when see real, you get destruction of virally infected cells)

Question 42

mRNA Vaccine

Answer 42

ex) Pfizer vaccine - same idea as Viral Vector vaccine, BUT rather than stick genetic material into a viral vector, you stick mRNA of gene - liposome (aq core - polar in middle & polar outside - bilayer & then packed with mRNA inside) - goes into body, finds host cell & does exact same as viral vector (ribosome does translation) - MHC I & spike Ag (secreted spike protein)

Question 43

For a mRNA Vaccine, how much spike protein gets secreted?

Answer 43

When ppl have adverse rxns, its going places idea: injecting in arm - from ECF, naturally go into lymphatic system - in LS, will activate immune cells there - IF leaves LS (not typical), then drains into blood & becomes systemically located - it can go anywhere & then have spike protein produced in other places & can bind SARS-COV-2 binds to ACE-II (BP mod.)