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chapter 5 Flashcards

1
Q

Smallpox Virology

A

Caused by a smallpox virus Poxviridae family
– ~ cowpox virus
– Large dsDNA genome: NCLDVs
– set up ‘second nucleus” in the cell cytoplasm
– enveloped (Golgi membrane-derived)

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2
Q

Edward Jenner

A

Vaccination
• Observed that milkmaids infected with cowpox were immune to smallpox

inserted pus, taken from a cowpox pustule, into an incision on child’s arm
– James Phipps later exposed to smallpox
à protected

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3
Q

Attenuated Vaccine example

A

Rabies, = virus weakened (mild or no disease)

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4
Q

Louis Pasteur did

A

Infected rabbits with rabies isolated from infected dogs

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5
Q

The ultimate goal of vaccines is to

A

induce memory immune response without causing diseases

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6
Q

Preventative Vaccine

A
  • Administered to an organism free of the targeted infection
  • Prepare the body (immune system) to possible infections
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7
Q

Therapeutic Vaccine

A

Administered to an organism already afflicted with an infection, against which natural (antiviral) immune responses are ineffective

Slow down and impede infections

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8
Q

Therapeutic Vaccination does

A

moderate effects of an existing pathogen

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9
Q

Therapeutic Vaccination is useful for?

A

Infections that can’t be cleared

Slow infections where symptoms develop a long time after infections

Vaccine used to boost immunity

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10
Q

Monoclonal antibody

A

1) Produce by ONE B cell population
2) Recognize ONE AND ONLY ONE antigen/epitope on the same molecule
3) very expensive to produce
4) no or low batch to batch variability

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11
Q

Polyclonal Antibody

A

1)Produced by different B cell populations
2)Can recognize multiple antigens/epitopes on the same
molecule
3) Relatively less expensive to produce
4) can have batch to batch variability

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12
Q

what does Therapeutic mAbs do?

A

it is monospecific

reduce the mouse ab immunogenicity

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13
Q

mab need to be re- engineered to become

A

chimeric ab (-ximab) humanized ab (-zumab)

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14
Q

Active Immunity (long term)

A

Natural: random/unintended exposure to infectious microbes

Artificial: Vaccination

Both humoral and cell-mediated immunity
Memory response

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15
Q

Passive Immunity (short term)

A

Natural: maternal antibodies
Artificial: from other sources

Only humoral immunity
No memory cells

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16
Q

what is Fetal/Neonatal Immunity

A

Only IgG can cross the placenta from mom to fetus.

Antibody production in newborns is very inefficient.
Maternal IgGs help protect them during the first 6 months of life.
Baby starts to produce its own IgG after 6 months.

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17
Q

What makes vaccines “good vaccines”?

A
  1. effective
  2. safe
  3. affordable
  4. stable with long shelf life
  5. easy to administer
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18
Q

what are Features of Smallpox that Enable Its Eradication

A

DNA virus

No intermediate host

Long incubation time

No persistent/latent infection

Easily diagnosed

Vaccine is safe, stable and inexpensive

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19
Q

what are obstacles for making a good vaccine?

A

Vectors, host intermediates and other susceptible
host species

multiple strains

Highly mutation rate

Varied genetic differences of the host
Maternal antibodies (???)
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20
Q

4 Types of Vaccines Used Today

A

Attenuated, live viruses

Whole, inactivated (killed) viruses

Capsid and subunit vaccines

DNA vaccines and
recombinant virus vaccines

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21
Q
  1. Attenuated Live Vaccines
A

Propagating the virus in semi-permissive cells/hosts or under altered conditions (low temperature) to produce virus particles which are able to replicate but at a reduced level (blind attenuation)
Pastorian approach
Louis Pasteur

22
Q

Jennerian vaccine

A

Vaccine derived from a virus different from the one it protects against

Now vaccinia virus is used as a smallpox vaccine (Edward Jenner)

23
Q

Attenuated viruses are often

A

often selected for by phenotype, with little to no knowledge of the changes in genotype.
Passages continue until a desired attenuation level is achieved, no matter how many passages take or how many mutations arise.

24
Q

FluMist:

A

is a live, attenuated flue virus with 4 strains

25
Attenuated Live Vaccines – Pros
Live vaccines are generally highly immunogenic. Activate both humoral (via MHC-II) and cell- mediated (via MHC-I) arms of the immune system Need less exposures for immunity Establish memory that lasts for years No adjuvant
26
Attenuated Live Vaccines - Cons
1. Chance of reversion to virulent strain 2. Not appropriate for immuno-suppressed individuals (ex. AIDS patients, very young and very old, cancer patients) 3. Virus must remain ‘alive’ during distribution and delivery 4. Adventitious contamination
27
Back mutation
attenuated viruses acquire ‘rescue’ mutations in individuals being immunized, picking up pieces of genome from the host, or recombination with similar viruses or types/strains
28
Oral Polio Vaccine (OPV)
- Polio virus (Picornaviridae) ssRNA (+) genome - 1963 OPV (mixture of three polio serotypes: 1, 2, 3) was licensed. - Showed evidence of reversion
29
what is Defined Attenuation
Genetically manipulate viruses | Introduce defined mutations
30
Inactivated Vaccines
Most successful form of vaccination in the early part of this century
31
Inactivated Vaccines pros
No chance of reversion to live strain Easier to store, refrigeration not necessary Virus is not able to replicate, this has consequences on how it is able to stimulate the immune system
32
Inactivated Vaccines cons
- Require higher dosing and additional boosts to generate useful levels of immunity - Cannot stimulate an MHC-I response
33
Capsid and Subunit Vaccines
- Immunogenic viral proteins or whole capsids - Made by purifying the viral protein from a virus preparation or by recombinant DNA cloning and expression of the viral protein in a suitable host cell
34
Capsid and Subunit Vaccines: PROs
``` -No chance for reversion – Not a complete virus being introduced -Stable storage -Fast to produce -Much easier to receive approval -Able to manipulate and optimize protein immunogenicity -Able to develop vaccines against ```
35
Capsid and subunit vaccines: CONs
- Not nearly as immunogenic as live or attenuated vaccines - Proteins are expressed by recombinant DNA technology may not be of correct structure - Does not induce a cell-mediated response - Requires a strong adjuvant - High mutation rates mean chimeric peptides or capsid vaccines are better than single protein vaccines
36
Hepatitis B Vaccines
Used to isolate virus particles from the blood of infected individuals and hepatitis B surface antigen (HBsAg) was purified -does not grow well in culture
37
HPV Vaccine
- Virus associated with cervical carcinomas - Whole capsid vaccine - Four serotypes of human papilloma virus - Recombinant HPV major capsid protein L1 from four HPV types mixed
38
Recombinant Virus Vaccines
Introducing the genes for immunogenic viral proteins into the genome of another, avirulent, virus
39
Recombinant Virus Vaccines Pros
carrier’ virus would be alive, allowing for a full repertoire of immune responses against ‘passenger’ protein ‘carrier’ virus could be modified to ensure absolute avirulency Candidate ‘carrier’ viruses  poxviruses, herpesviruses, adenoviruses (vaccinia used mostly)
40
Recombinant Virus Vaccines cons
Not clear whether the same level of immunity or repertoire of immune responses can be evoked from the expression of a ‘passenger’ protein ‘carrier’ virus can only be used once Some ‘carrier’ viruses considered have high preexisting immunity in the human population No vaccines against human diseases using this method are currently in production Newcastle disease in chickens
41
DNA Vaccines
- DNA coding for viral proteins under the control of a powerful promoter (IE-CMV) - Injected into muscle, induce the full range of immune responses
42
DNA Vaccines pros
Low risk, no virus particle present Easily manipulated, made, scaled up Easy to deliver and store dsDNA stimulates innate immune response
43
DNA Vaccines cons
- DNA is degraded quickly in the extracellular space | - ‘natural’ transfection rates are very low
44
Adjuvant 4 functions
Associates antigen with a particle, easier uptake by APCs Stimulates the immune response Localizes antigen at site of injection (depot effect) Can target antigens to particular pathways
45
MF59-Squalene pros
Stronger immunogenicity MF59 facilitates introduction of viral proteins into the cytoplasm of cells MHC-I antigen presentation! Cell mediated and antibody mediated immunity
46
MF59-Squalene cons
US veterans’ claims of autoimmune side effects | Later refuted, but stigma attached
47
Liposome vs Virosome
l: manufactured lipid bilayer, delivery system for transfecting proteins into cells v: liposome with virus proteins inserted, viral proteins into the cell cytoplasm
48
Insert DNA vaccine plasmid with eukaryotic promoters into
a bacteriophage | The virus would be taken up by APCs where the insert DNA could be expressed
49
DNA Vaccines pros
Bacteriophage DNA cannot be expressed in eukaryotic cells = safe DNA protected within a protein shell Induce innate immunity
50
Alternative Delivery Systems (3)
Oral administration Mucosal immunity Slow release
51
Herd Immunity
- When vaccination of a significant portion of the population (herd) provides a measure of protection for susceptible individuals - The greater the proportion of resistant individuals = smaller probability that a susceptible individual will come in contact with an infectious individual

Virology (6 decks)

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