12: vaccines Flashcards
Ways of defense agains viral diseases:
- general
- specific
- eradication
General way of defense agains viral diseases:
- surveillance and control
- monitoring of virus activity
- morbidity and mortality data
- case and outbreak investigations
- quarantines, restrictions, stamping out
- Animal hygiene
- feeding and keeping conditions
Specific way of defense agains viral diseases:
- in the environment:
- disinfectants
- in the host organism:
- antiviral drugs
- interferons
- immune sera
- vaccines
Resistance of viruses to environmental conditions:
- dehydration
- enveloped viruses
- high temperature
- protein denaturation
- 180C, 120C, 70C, 56C
- radiation (UV, gamma)
- damage of the nucleic acids
- Ionic environment
- optimal: pH 6.5-7.5
- limits: pH2-12
What are the aim of disinfectants and inactivating agents?
- virus inactivation in the environment
- vaccine production - preservation of antigenicity
Types of disinfectants:
- acid and bases (0.1M H2SO4, 3% NaOH)
- oxidants (H2O2, KMnO4)
- halogenids (iodine, chlorine, hypochloric acid, bleach)
- protein denaturants (ethanol)
- detergents, lipid solvents (chloroform, sodium deoxycholate)
- aldehydes (3% formaldehyde)
Types of inactivating agents:
- 0.001 % formaldehyde
- nucleic acid denaturants (EI, BPL)
Effects of antiviral medicaments:
- inhibition of virus replication
- decreasing the virus shedding
- localization of the infections
- -> but he infection remains
Problems with antiviral medicaments:
- close contact between virus and cell activity:
- effective drugs are often toxic for the cells
- -> specific agents are needed
- high viral mutation ratio: resistance
Types of Nucleoside analogues:
- First generation nucleoside analogues
- Second generation nucleoside analogues
First generation nuceoside analogues:
- incorporates into the nucleic acid
- more or less toxic - external use
- Iodoxuridine (IDU), trifluorothimidine (TFT),
Adenine-arabinoside (Ara.A)
–> topic ointments against herpes simplex - Ribovarin
What are Ribavirin?
- guanosine analogue
- mRNA guanyltransferae inhibitor
- against orthomyxo-, bunya-, arenaviruses
Second generation nucleoside analogues:
- activated by virus specific enzymes
- more selective to viral polymerase than to cellular
What are Acyclovir?
Acycloguanosine, Zovirax
- guanine derivate - acyclic “deoxyribose”
- viral TK enzyme phosphorilates
- selective to viral polymerase
- exonuclease does not remove = chain termination!
- effective against Herpes simplex virus-1, -2 nad Varicella-Zoster virus, but not against cytomegalo virus
What are Zidovudine?
Azidothymidine, AZT
- reverse transcriptase (RT) inhibitor
- ATZ-TP is competitive ti dTTP
- RT has no repair activity = chain termination!
- effective against retroviruses (HIV, HTLV)
Nonnucleoside RT inhibitors:
- directly inactivates RT
- Efacirenz, Delaviridine
- active against HIV-1
- used in combination therapies
Protease inhibitors:
- inhibits retroviral protease
- fits into the active center of the enzyme
- the cleavage of the precursor polyprotein is inhibited
- Ritonavir, Indinavir
- effective against HIV
What are Favipiravir?
T 705, Avigan
- RdRp inhibitor
- lethal mutations
- broad spectrum: effectiva agianst orthomyxo-, flavi-, alpha-, arena-, bunya-, entero-, filoviruses
Other antiviral drugs:
- Methisazone
- Amantadine, Rimantadine
- Neuraminidase inhibitors
= use of these in vetrinary practice is very rare! they are expensive, narrow spectrum, resistance occurs.
What are Methisazone?
- viral polymerase inhibitor
- against pox-infections
- poor solubility
What are Amantadine, Rimantadine?
- ion channel inhibitor
- uncoating is defected
- against influenza
What are Neuraminidase inhibitors?
- Oseltamivir (tamiflu)
- Zanamivir (Relenza)
- against influenza
Interferons, interferon inducers:
- high efficacy
- not antigen specific
- short effect
- parenteral administration
- expensive (species-specific)
- progressive hypo-responsiveness
- -> presently rarely used in veterinary practice
Immune sera and purified immunoglobulins:
- passive immunisation
- short term protection
- danger of serum-sickness or anaphylaxis
- large animas: enormous doses
- high costs (hyperimmunization)
- mainly in pet-practice: Canine distemper virus, canine parvovirus, canine adenovirus 1, feline panleukopenia, feline rhinotracheitis
- Goose parvovirus (Derzsy+s disease) - goslings.