Virology - Vaccines

Front 1

Simplest virus to remember

Back 1

-circovirus

Front 2

2 proteins of the circovirus

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-capsid
-replicase

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How is B-cell memory maintained?

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-follicular dendritic cells in the lymph nodes preserve antigen in its correct topological form, and must constantly present it to the immune system

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What can happen if Follicular Dendritic Cells are destroyed?

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-immulologic memory may get erased

Front 5

Virus that can hide in epidermis

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-papillomavirus

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Cancers associated with papillomavirus
-(species; cofactor)

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-Alimentary tract carcinoma (Cattle; bracken fern)
-Eye and Skin Carcinoma (Cattle; sunlight)
-Skin Carcinoma (Sheep; sunlight)

Front 7

Virus that can act a s a Trojan Horse

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HIV

Front 8

How does HIV act as a Trojan Horse

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-it can use a macrophage (APC) to bring the virus to its target (TH1), preventing CTL production

Front 9

How is influenza virus nomenclature determined?

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-HA, NA surface proteins
-virus type/species infected/location/year

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What are the mechanisms that an influenza virus uses to escape the immune system?

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-antigenic drift
-antigenic shift

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Influenza
-virus type

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RNA

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Types of mutations that can take place in an influenza virus

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-neutral mutation (3rd position codon change)
-negative mutation (non-functional proteins or poorly replicating viruses)
-positive mutations (changes in proteins that escape immunity)

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Number of antigenic sites associated with the HA protein

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-5

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Antigenic drift

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-a single or small number of changes to HA protein antigenic sites

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Antigenic Shift

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-replacement of most or all antigenic sites of the HA protein
-reults in a new H subtype

Front 16

What is the principle source of new flu virus subtypes for all species of animals?
-why

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Aquatic birds
-migration

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Why are pigs important in the spread of the influenza virus?

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-contain receptors for both human and avian viruses
-humans are unable to get the flu virus directly from the duck, but pigs act as a mixing vat, and make the virus transmissible between species

Front 18

Influenza NS1 Protein
-function

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-sequesters dsRNA and blocks the activation of PKR

Front 19

How is a virus with many viral proteins, such as the Alpha-herpesvirus, able to hide from attack?

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-Latency

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Latency
-how does it work

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-all virus transcription shuts down except for latency-associated transcripts (LATs)
-with less proteins being produced, there is less for the immune system to be able to attack
-can continue to divide while in latency, if located inside of a cell that is dividing

Front 21

Best vaccine for acute non-lethal infections

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-immunity from natural infection

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When would vaccination by natural infection not be ideal?

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-when the outcome of infection is death

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Requirement for vaccines to be effective

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-immunocompetent host

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Goal of a vaccine

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-provide protection

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Vaccine efficacy

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-ability to prevent disease
-induce an antibody response

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Vaccine safety

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-no undesirable side effects
-no reversion of MLV to virulence

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Vaccine approaches

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-infection with wild-type virus
-modified-live virus
-inactivated virus
-subunit formulation
-peptide
-DNA vaccine

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Vaccine
-desireable properties

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-stable
-no shedding of virus
-provides sterilizing immunity
-sustained protection
-contains a compliance marker
-contains a DIVA marker and a companion diagnostic test
-cost-effective
-resistanct to pre-exsisting blocking antibody

Front 29

Inactivated Virus Vaccine
-method of production

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-propagated in a culture system
-Inactivation with: formalin, heat, beta-propiolactone, UV light, irradiation
-Add adjuvant
-Tested for potency and safety

Front 30

Minimal vaccine

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-something that will form a trimolecular complex

Front 31

Inavtivated Whole Virus
-properties

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-stimulates humoral immunity only (TH2 response)
-safer
-more likely to cause allergic reaction due to adjuvant
-booster usually required
-slower onset of protective immunity
-may not stimulate strong/long-lasting immunity
-susceptible to blocking by pre-existing antibody
-disease outbreak can be caused by incomplete inactivation
-contamination

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What is key to prevent infection with inactivated vaccines?

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-induction of humaral immunity

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Why is there a narrow window of vaccination for inactivated virus vaccines?

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-pre-existing antibody (maternal antibody) can block vaccination through sequestration
-animal will eventually become exposed to disease
-need to avoid blocking antibody, but be ahead of natural exposure

Front 34

Live Virus vaccine
-what are they

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-replication competent vaccines that will establish infection in the host, but are less likely to cause disease

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Live Virus Vaccine
-types

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-naturally occuring avirulent virus (cowpox)
-attenuated modified-live virus
-genetically engineered wild-type

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Attenuated Modified-Live Virus
-formation

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-virulent wild-type virus that was serially passaged in an unnatural host

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Genetically Engineered wild-type virus
-formation

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-virus that has had its virulence gene removed to make a MLV

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Difference in dosing between an inactivated virus vaccine and a MLV

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-killed virus vaccine usually requires multiple doses in order to gain immunity
-MLV usually only requires 1 dose

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MLV examples
-Virus (culture cells)

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-Rabies (monkey kidney cells)
-Canine Parvovirus (feline kidney cells)
-Feline Herpesvirus (feline kidney cells)
-Infectious Laryngotracheitis Virus (chicken kidney cells)

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Reason why MLVs are more efficacious

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-TH1 arm of the immune system is stimulated and CTLs have the ability to recognize cells infected with the MLV
-TH2 arm is also stimulated

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MLV
-properties

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-may cause moderate-severe clinical disease (especially in pregnant animals)
-possible reversion to virulence
-unstable
-can cause persistent infection
-cannot always differentiate between vaccinated and infected animals
-may require cold chain or on sitee preparation

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Why are pregnant animals at risk of contracting a moderate-severe clinical disease from MLVs?

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-immunocompromised

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One of the most successful vaccines in veterinary medicine

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-rinderpest vaccine

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Rinderpest vaccine
-vaccine type

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-MLV

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Has Rinderpest been totally eradicated?

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-probably not
-probably within wildlife reservoirs

Front 46

Subunit vaccine

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-viral proteins separated from the whole virus
-just provide the essential proteins to induce an immune response

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Subunit vaccine
-how to make

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-mechanical or chemical treatment of an inactivated virus
-recombinant techniques

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Subunit vaccine
-properties are most similar to

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-inactivated vaccine

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Subunit vaccine
-advantages

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-increase subunit mass
-incorporate tests to differentiate infected from vaccinated animals (DIVA)

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DIVA

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Diferentiate Infected from Vaccinate Animals

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DIVA
-function

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-different types of proteins are present on the surface of a virus
-create a subunit vaccine to one of the antigens on the cell surface
-after vaccination, only antibody to the subunit vaccine will be made and not to other antigen from the cell
-if after the vaccination of the subunit vaccine there are antibodies present from all of the surface proteins of the virus, then you know you have natural infection

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Why is DIVA important?

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-helps to identify if there is vaccine failure (virus mutation)
-compliance

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Maximum Safety
-vaccine type

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-innactivate vaccine
-subunit vaccine

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Maximum efficacy
-vaccine type

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-live virus vaccine

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Vaccine
-formulation

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-antigen
-stabilizers
-adjuvant

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Adjuvant
-function

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-retains antigen for slow release to the immune system
-activates TLRs
-initiates a low-grade inflammatory response