Virology lecture 5 Flashcards
public health control measures?
1 - quarantine/isolation/slaughter - used with vaccination for smallpox. used with surveillance for rinderpest and FMDV, then slaughter of infected herd. also rabies
2 - surveillance - allows rapid containment of an epidemic - influenza, measles, rubella and AIDS
3 - Vector control - ie pesticides for urban mosquitos for YFV and dengue virus.
4 - screening blood and blood products - rigorous.only possible when we know the existence of the patholgen ie HIV, HBC, HCV.
Smallpox caused by?
identification vs chickenpox?
death rates?
1 - variola virus.
2 - centrifugal distribution of pustules (face and trunk predom) rather than even coverage of lesions.
3 - variola major virus = 30-40% deaths in unvaccinated pop. variola minor virus (alastrim) = 1% mortality (which is still bad).
what is variolation?
1 - also known as inoculation. take pustular material from smallpox survivor containing live virus and inoculate into the skin. 1% mortality rather than 30-40% via respiratory infection. 1723
who invented vaccination and when?
name of cowpox virus?
milestones
1 - edward jenner in 1796
2 - took until 1980 to eradicate it due to vaccine supply and demand issues
3 - 1939 UK free of smallpox
4 - cowpox vaccine = vaccinia virus
5 - 1950 - freeze dried vaccine - easy to transport without loss of potency
6 - 1967 - use of ring vaccination = surveillance, vaccination and quarantine.
7 - 1977 last naturally occuring case in somalia
8 - 1980 - WHO certified eradication
why was smallpox suitable for eradication?
1 - no animal reservoir. vs rabies or YFV
2 - infection was acute not latent or persistent. vs herpes
3 - easily recognised. vs HIV
4 - vaccine was effective against all strains as no antigenic variation due to high fidelity DNA dep DNA pol.
5 - vaccine potent as single dose, cheap, abundant, heat stable when freeze dried, easy to administer, induced both cellular and humoural immunity.
6 - the determination of the WHO.
rinderpest virus, mech of eradication, dates, key name
1 - rinderpest virus
2 - domestic cattle, buffalo and related ungulate epidemics. devastating.
3 - controlled by live vaccination developed by Walter Plowright.
4 - last case 2001, certified eradication in 2011.
rabies progression, vaccine development
1 - slow progression as it travels up nerves from bite site to the brain, post exposure vaccination is effective. The more distal the bite the longer you have.
2 - pasteur developed it from dried infected rabbit spinal cord in 1885.
3 - now grown in cell culture and inactivated by beta-propriolactone.
YFV vaccine?
1 - 1937 Max theiler - live attenuated vaccine, retains infectivity but loses virulence. still used.
influenza vaccine first production and current method
1- 1942
2 - subunit vaccine, grow virus in eggs, purify HA and NA and use these as the immunogen with an adjuvant.
polio vaccine
1 - first porduced 1954 by Salk. purified virus, chemical inactivation
2 - 1956 - Sabin, live attenuated vaccine for the 3 serotypes by serial passage. these can be given orally
MMR vaccines
1 - live attenuated for measles 1960, rubella 1966, mumps 1967. passaging the wild virus then isolating the attenuated remains. now given together as MMR.
HBV vaccine?
1986 - genetically engineered (the first). express the surface antigen HBsAg in yeast, purify, inject with adjuvant.
HPV vaccine
2006 - genetically engineered for HPV strains 16 and 18. givne in UK prior to puberty.
the three types of vaccine?
1 - live
2 - dead
3 - passive immunization
live vaccine deets and adv and disadv. examples.
either attenuated mutant or live related virus.
1 - attenuated - YFV, measles, mumps, rubella, polio (sabin’s version), VZV, canine distemper virus, pseudorabies virus (pig herpes - genetically engineered deletion mutant), rinderpest virus.
2 - live related - vaccinia cirus for smallpox (nb caused by variola virus), turkey herpes virus for Marek’s disease (tumour inducing virus in chickens),
3 - adv - self replicating so cheaper, induce both cellular and humoural immunity that is long lived.
4 - disadv - occasionally it can become virulent again , can cause issues in immunocompromised patients, cold storage needed for most. Salk (killed) vs Sabin (live) vaccines for poliovirus.
dead vaccine deets, adv, disadv, examples.
either whole viruses that have been purified and inactivated (poliovirus, Salk’s version), or subunit vaccines isolated from the whole or via genetic engineering (HBV, HPV).
also HAV, rabies, FMDV, influenza.
1 - adv - safety as not infectious
2 - disadv - require multiple administrations to achieve adequate immunity, only AB response not cullular. may need adjuvant. less effective. The cutter disaster with polio vaccine in the USA?
passive immunization - deets, examples, adv, disadv
administer antibodies targeting the pathogen. originally serum from immunised animals but being replaced by human MAB. eg after exposure to rabies or HBV (neonates). maternal antibodies via breast milk.
1 - adv - immediate protection even post exposure
2 - disadv - serum sickness with serum, short lived protection, immune response to the MAB.
new approaches to vaccine development?
1 - rational attenuation - specific virus gene modification or deletion to remove virulence. NB a deletion mutant cant revert. pseudorabies virus (herpes virus in pigs), delete thymidine kinase
2 - vector mediated sub-unit delivery - introduce a gene for a subunit vaccine into a live yet safe viral vector. rabies glycoprotein into vaccinia virus. can create polyvalent vaccines by incorporating multiple genes.used to immunise foxes in western europe against rabies.
3 - virus-like particles - capsid proteins for icosahedral capsids will spotaneously assemle. synthesise them and they can induce an immune response as they contain the anitgen but contain no nucleic acid. used for HPV16 and 18 vaccine.
4 - nucleic acid immunization: prime-boost - inject the DNA encoding the desired antigen under a strong promoter. then boost with a live virus vector expressing that same antigen.
antiviral chemotherapy principles and targets
target specifc virus enzymes as most use host enzymes which would cause side effects. target nucleic acid polymerases, proteases, influenza virus NA and HIV integrase
1 - AZT, azidothymidine, thymidine analogue, vs HIV. phosphorylated to dNTP, incorporated by reverse transcriptase into the viral DNA, no 3’ hydroxyl so causes termination. specificity as cell DNA pol dont use it effectively.
2 - Acyclovir (zovirax), not phosphorylated by cell kinases but is by HSV thymidine kinase, incorporated and terminates chain growth.
3 - HIV protease inhibitors - several that are specific to HIV protease, prevent formation of mature gag and pol
4 - oseltamivir phosphate (tamiflu) - an analogue of sialic acid, inhibits influenza NA so it cant be released from the infected cell, also causes viral aggregation as HA and NA are glycoproteins, preventing dissemination.
