Med Micro 8 - Vaccines Flashcards

1
Q

What is a vaccine?

A

suspension of attenuated or killed microorganisms, or of antigenic proteins derived from them, administered for prevention, amelioration, or treatment of infectious diseases

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2
Q

Types of vaccines

A

Attenuated (live - attenuated virulence), Killed (inactivated and avirulent), Toxoid (inactivated and avirulent), Others (nucleotide, conjugate, Viral like particle)

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3
Q

Attenuated

A

Weakened so they cannot cause disease. Stripped of essential virulence factors, heat killed, etc.

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4
Q

What type of vaccine would you use to generate as large an immune response as possible? What cell would you target? How?

A

It is an open question. One way: target APC with attenuated vaccine. It stimulates release of cytokines, chemokines, interleukin, GF, so antigens will be presented to T helper cells to activate adaptive immune response. Polyclonal response

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5
Q

What would you do if you couldn’t produce an attenuated vaccine to generate as large an immune response as possible? What cell would you target? How?

A

It is an open question. One answer: Target a Pro APC using a PAMP with a linked specific antigen (conjugated vaccine). Stimulates the immune response.

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6
Q

Changing face of vaccine development

A

Conventional development and reverse vaccinology

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7
Q

Conventional vaccine development

A

take some pieces of a pathogen (ie flagella, cell surface), test in convalescent sera, test immunogenicity (agglutination), purify, identify, clone genes, test in animal models. 10-15 years

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8
Q

Reverse vaccinology

A

aka reverse genetics. Based on DNA, identify potential candidates based on homology and function (computer prediction). Way faster.

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9
Q

Convalescent sera

A

Serum from someone recovering from a disease. They have Ab so you can test.

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10
Q

Why is ELISA so important?

A

Test for Ab binding an antigen. If people have the Ab, they’ve been exposed to the antigen

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11
Q

Use of LD50?

A

Not so good to identify pathogen etc; Tell you whether or not vaccine candidate is protective

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12
Q

Hydropathy plots

A

help us know where in membrane. Can focus on one place and make conjugated vaccines.

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13
Q

Process of attenuation for virus (classic)

A

Isolate virus from infected human and grown in human tissue culture; grow in tissue culture of another species; virus gains mutations to grow there, but no longer can infect humans

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14
Q

Process of attenuation for bacteria (classic)

A

Culture under weird conditions or genetic manipulation

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15
Q

Attenuated vaccine - reverse genetics method

A

Insert genes from a virulent strain into a the coat of a non-virulent strain ***

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16
Q

What is a potential concern with vaccines even if they are avirulent? Why?

A

May generate an allergic reaction (rare) or inflammatory response,

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17
Q

Killed/Inactivated Vaccine

A

Deactivated whole microbes or subunit. When killing we need to maintain antigen structure. Formaldehyde - causes cross-linking of proteins and nucleic acids

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18
Q

Adjuvants

A

Goal is to stimulate an immune response. Ex. slow down processing of antigen so immune response has more time to be activated

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19
Q

Elements of gene

A

Start site (Met), stop site, promoter (RNA polymerase binding), transcriptional start and stop, translational start and stop (not same as transcript), regulatory sequences (operator - b/w promoter and start, used to stop RNA poly). Genes produce polypeptide.

20
Q

Do all genes have a promoter?

A

No, operons are several genes but have only one promoter

21
Q

How do we express a gene outside of its normal host?

A

Plasmid in E. coli for example.

22
Q

How do we express the protective parts of a gene?

A

Cut out parts that will be exposed on outside, then link the piece to other pieces or something else. Need a promoter

23
Q

How can we define what parts of a gene would be protective?

A

Something that is exposed that the immune system would recognize if there was an infection, so we can protect ourselves against it. Hydropathy plots.

24
Q

If protective parts are too small to make a immune response what do you do?

A

Make conjugate vaccines! Lots of

25
Q

How would you develop a new Influenza vaccine knowing that it mutates so fast? (final exam question)

A

Look for something that is very conserved

26
Q

Consider the different route of administration of the two flu vaccines, and then type of immune response each would generate

A

Live attenuated: given nasally, infects through normal route; creates humoral and cell-mediated response (to kill infected cells). Killed: only antibody (humoral) response; prevents spreading to new cells

27
Q

Diagram killed whole cell vaccine

A

??

28
Q

Toxoid (inactivated) vaccines

A

chemically or thermally modified toxins. Must try to retain original shape. Generates what type of response???

29
Q

Why is attenuated better than toxoid

A

??

30
Q

HIV subunit vaccines

A

Inactivated HIV subunit vaccines do not maintain their 3D structure; and it changes its antigens so rapidly that we cannot form vaccine

31
Q

Heptavalent conjugate vaccine (polysaccharide)

A

7 components against 7 strains with slightly different polysaccharide attached to a protein (for S pneumoniae)

32
Q

What kind of immune response would subunit vaccine generate?

A

Antibody response (T-dependent humoral). Won’t infect cells, just get taken up.

33
Q

Polynucleotide vaccination

A

Taking the DNA that codes for a pathogen’s antigen and put it in a DNA plasmid, which is injected into a patient’s cell. Presented on MHCI (could use another gene to be exported too…) so cell-mediated.

34
Q

Pros of attenuated vaccine

A

Lots and lots of epitopes - huge response and long lasting. Normal pathway. Possibly mild infection but no disease. Viral ones cause cell-mediated and humoral response. Vaccinated individuals can infect those around them with the attenuated virus (contact immunity)

35
Q

Cons of attenuated vaccine

A

Possible for vaccine to revert or and begin to cause damage again. Can only enter host cells. Not suitable for certain people (age, pregnant, immunocompromised)

36
Q

What kind of response would an attenuated vaccine cause?

A

Virus can infect cells, just no damage. So largely a cell-mediated response (Th1 and Tc)

37
Q

Pros of killed vaccine

A

Safer (subunit and whole cell)

38
Q

Cons of killed vaccine

A

Weak antigenically. Can cause allergic responses (adjuvants), especially with high or multiple doses (ie second and third time gets worse) - if not cleared by adaptive immunity, innate immune response is

39
Q

Pros of conjugated vaccine

A

Safer, not monoclonal

40
Q

Cons of conjugated vaccine

A

Not as strong of a polyclonal response (fewer epitopes) - require booster shots sometimes. Doesn’t affect via normal route.

41
Q

Pros of subunit vaccine

A

Can protect against several strains by targeting a common subunit

42
Q

Pros of Polynucleotide vaccination

A

inexpensive, safe, induces broad range of immune responses, long lived immunity

43
Q

Cons of Polynucleotide vaccination

A

Integration into DNA (hasn’t happened yet), Limited to protein vaccines, autoimmunity (not yet)

44
Q

How does polynucleotide vaccination induces a broad range of immune responses? Be able to show this

A

Broad = cell-mediated and humoral. Transcript translated in cytoplasm causes cell mediated immune response; use another gene to be exported to outside would generate humoral.

45
Q

What type of immune response does each vaccine type cause?

A

Working on it

46
Q

Reverse genetics

A

Delete virulence gene - cannot revert; express in yeast etc.; ex HPV gardasil - VLP has some components but not complete virus, vaccine delivery system - goes through main expression, cause cell-mediated

47
Q

Active vs passive immunization

A

Active: get disease, vaccination; passive: injection of antibodies produced commercially (antitoxins); we generate response against passive Ab; can be contaminated with viral pathogens; short lived