Lecture 6: Prophylaxis and therapy of viral infections Flashcards

1
Q

What is important to note about vaccination plans?

A

You need to make your own. Dont rely on others.

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2
Q

Who created the first vaccine? How?

A

Edward jenner -> Cowpox for small poxs

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3
Q

What are the categories of protection from viruses?

A
  • Interferons and interferon inducers
  • Viral vaccines
  • Chemotherapeutic agents
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4
Q

What are the 3 categories of vaccines?

A

I -First generation (conventional vaccines)
II-Second generation vaccines
III-Third generation vaccines

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5
Q

What kinds of vaccines are part of First generational / conventional vaccines?

A
  • Live attenuated vaccines
  • Heterologous viral vaccines
  • Inactivated viral vaccines
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6
Q

What kinds of vaccines are part of Second generation vaccines?

A
  • Subunit vaccines
  • Genetically engineered vaccines
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7
Q

What kinds of vaccines are part of third generation vaccines?

A

DNA vaccine

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8
Q

Are emergency vaccines for infected animals?

A

No they are for at risk animals, not infected animals.

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9
Q

What are the purposes of vaccinating? What time frame should you be vaccinating for :?

A
  • To render the virus non infectious without destroying its antigenicity/immunogenicity
  • Prophylaxis: vaccine is given to animals to protect them against some expected viral diseases
  • Protection of newborn animals: pregnant animals are vaccinated to transfer the passive immunity to their offspring
  • Vaccines must be given in advance before expected infections with reasonable time to allow the immunity to develop ( takes 1-2 weeks to develop an immune response)
  • Vaccines may be administered during an outbreak with some viral infections in an attempt to protect the non infected animals at risk
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10
Q

What is the criteria for an ideal vaccine?

A
  • Produce some kinds of solid immunity (long lasting)
  • Produce an early protective immunity
  • Provides protection against pathogen variants
  • Produce a life long immunity preferably in a single dose
  • Prevents infection
  • Do not produce any carrier state in vaccinated animals
  • Can be administered by mass immunization • Safe and stable
  • None or minimal side effects in the vaccinated animals ( enough to stimulate immune system but not enough to debilitate animal)
  • To be fit for a long term storage vaccine banks
  • Thermostable to avoid cold chain
  • Differentiation between infected and vaccinated individuals (DIVA)
  • Cost Effective
  • Produced inexpensively and in large quantities
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11
Q

What is DIVA?

A

A system to tell if an antibody is via natural infection vs. vaccination. A marker is applied to a component in a vaccine so you can tell if the patients antibodies are via vaccine.

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12
Q

What is an attenuated vaccine?

A

Vaccine made less virulent

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13
Q

What is a killed vaccine?

A

Vaccine of a killed virus, this will still stimulate the immune system.

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14
Q

What vaccine is the most ideal?

A

Killed vaccines

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15
Q

What is a subunit vaccine?

A

Nonrecombinant purified part of virus

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16
Q

What is the benefit of a clone vaccine?

A

You can make a competent viral vector vaccine, DNA vaccine, or use proteins to make a virus like particle vaccine vs. a subunit vaccine

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17
Q

What is the types of active immunity? Passive immunity?

A

Active:
- Natural infection
- Vaccination
Passive:
- Maternal immunity
- Hyperimmune sera

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18
Q

What are the requirements to develop protective immunity against viral infection?

A
  • IgG, IgA, CTL
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19
Q

Where can you find IgA?

A
  • Submucosa, vagina, digestive tract, ect ( bodily secretions)
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20
Q

What is the primary protective immunity?

A
  • Abs in the blood (IgG) immune
  • IgA (mucosal surfaces)
  • Cell-mediated immunity (Tc)
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21
Q

What is the systemic infection protective immunity? *** mean the magnitude of each

A
  • IgA*, IgG***, Tc ***
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22
Q

What is the local infection protective immunity? *** mean the magnitude of each

A
  • IgA***,Tc***, IgG*
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23
Q

What are the important considerations for a vaccine?

A

Design parameters, safety and efficacy, practical considerations.

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24
Q

What are the practical considerations for a vaccine?

A

Economical/Ease in handling
• Multivalent, one-shot
• Low cost of production
• Stable
• Needle-free delivery

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25
Q

What are the design parameters to be considered for a vaccine?

A

• Clear understanding of pathogenesis
of the target virus
• Consider characteristics of the virus for selection of vaccine type and delivery route
• Cellular vs humoral immunity, or both
• Mucosal vs parenteral vaccination or both
• 90% of all viruses enter through
mucosal surfaces

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26
Q

What are the safety and efficacy considerations for vaccines?

A

• Effective in newborn animals
• Minimal adverse reactions
• Minimal tissue damage
• Safety in pregnant animals
• Induction of both humoral &
cellular immunity
• Mucosal immunity
• Long-term memory

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27
Q

What are the principles of a live attenuated vaccine?

A

Weakened viruses under lab conditions.
They will grow in a vaccinated individual but because they are weak they will cause no or very mild form of the disease,

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28
Q

What are some examples of attenuated vaccines?

A
  • Oral polio vaccine (OPV)
  • Measles
  • Rotavirus,
  • Yellow fever
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29
Q

What are side effects of live attenuated vaccines?

A

Revert to virulence and causing the original form of diseases of the wild type virus in some cases
• Potential harms to the immunocompromised personnel
• Contaminated cell culture vaccines: Rota virus and Measles virus if grow in cell culture
• Not recommended in case of pregnancy

30
Q

What immune response occurs with live attenuated vaccines?

A
  • Stimulates the production of excellent immune response. ( Humoral + CMI) similar to wild type virus
    Stimulates production of memory cells
31
Q

How do they grow live attenuated vaccines so that it can be controlled?

A

Passage the wild type virus in a unnatural host
• Passage of the wild type virus in unusual conditions

32
Q

How does passage of the wild type virus in an unnatural host affect the vaccine?

A

By continued passage of the wild type virus in unnatural host- progressive adaptive mutations - virus adapts to new host- retain their capacity for transient growth within an inoculated natural host.

33
Q

How does growing a pathogenic virus under abnormal culture conditions affect the vaccine?

A

– By growing a pathogenic virus for prolonged period under abnormal culture condition- select mutants better suited to growth in the abnormal culture conditions and less capable of growth in the natural host.

34
Q

What are the advantages of live attenuated vaccines?

A
35
Q

What are the disadvantages of live attenuated vaccines?

A
36
Q

What are examples of live attenuated veterinary vaccines and where they were created?

A

• Canine parvovirus (CPV): feline kidney cells

  • Feline herpesvirus (FHV): feline kidney cells
  • Infectious laryngotracheitis virus (ILT): chicken kidney cells, embryonated chicken eggs
37
Q

What are heterologous viral vaccines? What are some examples?

A

• Principles: two viruses that are antigenically related to each others thus protection arise from the presence of
the cross reacting antigens

• The heterologous vaccines are naturally attenuated

• Examples of heterologous vaccines
-Pigeon poxvirus protects against Fowl poxvirus

  • Shop fibroma virus rabbit protects against Rabbit myxomatosis
  • Sheep-pox virus protects against Lumpy skin diseases virus (LSDV)
  • Herpesvirus of turkeys (HVT) protects against Marek’s diseases virus (MDV)
  • Rinderpest virus (RPV) and measles virus protects against Canine distemper virus (CDV)
38
Q

What are inactivated or killed viruses? What are the methods of killing the virus?

A

Whole virus inactivated or propogated via physical or chemical methods.

Physical methods: Formalin, Heat, beta propiolactone

Chemical methods: UV, irradiation.

• Virus does not replicate in the vaccinated animals requires a larger
antigenic mass

  • Va c c i n e may be expensive to produce
  • Requires an adjuvant to enhance the magnitude of the immune response
39
Q

What are the advantages of inactivated/ killed vaccines? How do they work?

A

These agents inactivate the viral nucleic acids without affecting the capsid or envelope proteins against
them the antibodies are produced
- They are relatively stable, safer especially in pregnant animals, minimal post vaccine rxns, possibility of spread is rare.

40
Q

What are the diadvantages of inactivated/ killed vaccines?

A
  • very expensive ( made from highly concentrated virus)
  • short term immunity, needs booster doses
  • less efficient in induction of CMI
41
Q

What are the kinds of Adjuvunts and their modes of action?

A

Depot adjuvant: Causing depot formation at the site of injection - For example, mineral compounds, oil-based adjuvants, liposomes

  • Particulate adjuvant: Acting as delivery vehiclesfor the antigens, which may help in targeting antigens to immune
  • Immuno-stimulatory adjuvant: ISCOMs: are 40 nm large particles made up of saponins (Quil A), lipids, cholesterol and antigen, held together by hydrophobic interactions between the first three components
  • Freund, in 1937, demonstrated the adjuvant effect of mineral (paraffin) oil mixed with killed Mycobacteria, referred to as Freund’s complete adjuvant (FCA).
  • The water-in-oil emulsion without Mycobacteria, known as Freund’s incomplete adjuvant (FIA), has been used in a number of veterinary vaccines.
42
Q

Wah is an adjuvant?

A

Def: a component that potentiates the immune
response to an antigen and/or modulates it
towards the desired immune response.

43
Q

What are the effects of an adjuvant on the immunogenicity of viral vaccines?

A
44
Q

How are inactivated vaccines administered and what immune response does it have in each location?

A

Inactivated vaccines (parenteral route):

  • Administered I/M or subcutaneous routes only
  • Generates IgG only,
  • no cellular immunity –
  • protective immunity for systemic infections associated with viremia; to lesser extent local infections.
45
Q

How are live vaccines administered and what immune response does it have in each location?

A

Live vaccines:

• Administered in the mucosal surfaces (Intranasal, oral or genital)

▪ IgA (mucosal immunity), IgG, cytotoxic T cells Protective immunity for both systemic and local infections

• Administered by parenteral routes (I/M, sub cut)
▪ IgG and Tc but no IgA

46
Q

What is the main difference between live virus and killed virus vaccines in terms of immunity?

A

Live virus: one dose can be protective) amplification of injected dose occurs)

Killed virus: Multiple doses are necessary for protection

47
Q

What are the Common disadvantages of the conventional viral vaccines?

A
  • Reversion to virulence
  • Incomplete inactivation
  • Contaminations
  • Secondary effects
  • Inflammation, granuloma, fever, hypersensitivity
  • Immuno-suppression
  • Inability to differentiate vaccinated from infected animals
  • Cold-chain requirement
48
Q

What are subunit vaccines? What is an example of this?

A

Split virus products: viral proteins separated from virus-infected cells via mechanical or chemical treatment

49
Q

What are the types of recombinant vaccines and how do they work?

A
50
Q

What is the advantages of a subunit vaccine?

A
  • Prepared from virus components devoid from viral NA such as capsid and envelop proteins
  • These components are responsible for the induction of the immune response against the virus of concern

• Advantages of the subunit vaccines
- It is safe because it is free from NA -It does not induce febrile reactions which induced by some proteins in the other viruses -It is highly immunogenic in high doses

51
Q

What is a genetically engineered subunit vaccine (single gene)?

A
  • Virally vectored subunit vaccine
  • Plasmid based/vectored subunit vaccine
  • expressed in bacteria
  • expressed in yeast and mammalian cells
52
Q

What are DNA Vaccines?

A

These vaccines are based on the introduction of a DNA plasmid into the host cells The plasmid carries a protein-coding gene that transfects cells in vivo at very low efficiency and expresses an antigen that causes an immune response.

53
Q

What are the delivery methods of DNA vaccines?

A

• Injection of the prepared DNA vaccine in saline solution

  • Intramuscular (IM)
  • Intradermal (ID)

-May be assisted by the electroporation method
• Gene gun delivery approach

54
Q
A
55
Q

What are the advantages of DNA vaccines?

A
56
Q

What are the disadvantages of DNA vaccines?

A
57
Q

What is the distribution of protective immune response in vaccinated animal populations

A

Usually occurs as a bell curve. No vaccine is expected to produce 100% protection

58
Q

What is maternal immunity? How long do serum IgG antibodys last in young animals?

A

• Maternal immunity
- passive transfer of humoral immunity via colostrum/milk/egg yolk

  • protection of newborn and young animals
  • prevention of enteric infections
  • No cellular immunity and lacks memory immune cells.
    • Example:
    -Transmissible gastroenteritis virus (TGEV) infection of pigs. -Corona and Rotavirus infections in calves.
    • Vaccination of young animals: Serum IgG antibodies persist for :
  • up to 6 months in cattle, horses
  • up to 4 months in dogs, cats, pigs
  • up to 1 month in chickens, turkeys
59
Q

What are ways we can overcome the effects of maternal antibodies? Why do we need to do this?

A
  • To do repeated vaccinations before the predicted loss of antibody
  • Using the intranasal route (mucosal) when modified live vaccines are used
    We do this because maternal antibodies interfere with immunization of young animals.
60
Q

What are some causes of vaccine failure?

A
  • Wrong strain/serotype of organisms
  • Method of production destroy protective epitopes - inactivated vaccines

• Failure of an effective vaccine to stimulate protective immunity may be due to:
1. Unsatisfactory administration

  1. A live vaccine may have died
  2. Timing - Vaccination Schedules - Lag time
  3. Animal to animal variability
61
Q

What can cause vaccine reactions and what reactions can you see?

A
62
Q

What is a ring vaccine strategy?

A

• The vaccination of all susceptible herds in
a prescribed area around an outbreak of
an infectious disease

• Ring vaccination controls an outbreak by
vaccinating and monitoring a ring of
herds around each infected herd

• The idea is to form a buffer zone of
immune herds to prevent the spread of the
disease

63
Q

What is heard immunity?

A

• Herd immunity is achieved when large number of individuals become immune against circulating infectious diseases

  • Herd immunity restrict the spread from person to person
  • Herd immunity can be achieved when Large number of community either recovered from infection or vaccinated against certain infectious diseases

• In some research, herd immunity may be achieved if up to 70% of the population are immune (recovered/vaccinated)

64
Q

What occurs during the typical human/ animal vaccine pipline?

A
65
Q

What are some SARs-CoV- 2 vaccine candidates?

A
66
Q
A
67
Q
A
68
Q

What is the design of some SARS-CoV-2 mRNA vaccines?

A
69
Q

How does the pfizer- biotech covid 19 vaccine work/ mechanism of action?

A
70
Q

What is the immune response to Sars Cov-2 mrna vaccines?

A
71
Q

What are some common challenges in the veterinary vaccine sector?

A

• Cost Effectiveness economy of vaccine production

• Diseases where vaccine is most demanding - Classical swine fever, sheep and goat-pox,
bluetongue, FMD, EHV-1/4, strangles, haemorrhagic septicemia (HS), etc

  • Vaccine updating: many RNA viruses (FMD virus, bluetongue virus, and influenza viruses) are highly variable and require updating of vaccine very frequently
  • Potency Testing batch potency tests - involve administration of vaccine to target species or laboratory animals

• Viruses with genetic heterogeneity, high mutation rates and quasi-species are difficult targets for
vaccination: porcine respiratory and reproductive syndrome virus (PRRSV), Retroviruses, bovine viral
diarrhea virus (BVDV)

•Cellular immunity and long-term memory often difficult to be achieved

72
Q
A