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5 types of public health control measures
- quarantine/isolation/slaughter eg with smallpox, rabies
- surveillance: notifiable diseases eg influenza, measles, rabies, AIDS. Allows swift action eg vaccination/anti-viral drugs
- sanitary engineering/food hygiene regulations: polio and Hep A spread by faeco-oral route
- vector control: eg yellow fever spread by mosquitoes
- screening of blood and blood products: Hep B and C, HIV
what virus causes smallpox?
2 strains of variola, mortality difference
- variola major: 30-40% mortality
- variola minor aka alastrim: 1% mortality
visual difference between smallpox and chickenpox
smallpox more centrifugal (pustules more abundant on face than trunk)
first measure for controlling smallpox
variolation: injection of pus under skin
what is ring vaccination?
Vaccinating people in close contact with the disease to prevent it spreading
Why is variola virus still under testing? (2)
- developing a safer vaccine
- drugs that prevent smallpox because of the fear of bioterrorism
6 reasons why smallpox eradication was possible
- acute disease
- no animal reservoir
- easily diagnosed
- WHO determination
- good vaccine: potent at single dose, low cost, abundant, heat stable, easy to administer, induced both cellular and humoural immunity
- no antigenic variation
what is the only other infectious disease to have been eradicated?
Rinderpest, by vaccination
What did Pasteur produce vaccines for in 1885? (2) how?
- Anthrax and rabies
- drying spinal cord of rabbits with rabies so that infectivity had pretty much gone but virus antigen remained
How is rabies vaccine produced now?
- Grown in cell culture
- treated with B-propriolactone to inactivate virus infectivity
How did Theiler produce a vaccine for yellow fever?
Passing virus multiple times: retained infectivity but had lost virulence - 1st live attenuated vaccine
How are influenza vaccines produced now?
Grown in eggs, purifying HA and NA and using these with an adjuvant: a subunit vaccine
How were the 2 types of polio vaccines created?
- Salk: purification, chemical inactivation, injection
- Sabin: serial passage - live attenuated
What was the first genetically engineered vaccine? How was it made?
Hep B: expressing Hep B surface antigen (HBsAg) in yeast, purifying, and injecting with adjuvant
2 types of live vaccines, with examples. Pros and cons.
- Attenuated mutants of wild type (yellow fever, MMR, Sabin polio)
- live related: vaccinia for smallpox, turkey herpes virus for Marek's disease (chicken tumours)
- Pros: cellular and humoural immunity, self replicating (cheaper), long lived
- Cons: can mutate to become virulent, may be dangerous in immunocompromised hosts
2 types of dead vaccines, with examples. Pros and cons.
- Purified and inactivated whole virus preparations (Salk polio)
- subunit vaccines from whole vaccine/genetically engineered parts (influenza, HBV, HPV)
- pros: safe
- cons: multiple injection, only antibody responses (not cellular)
describe passive immunisation
- administration of antibodies (human monoclonal)
- eg after exposure to rabies or HBV as neonate
- pros: immediate protection
- cons: serum sickness (formerly), short lived
4 new approaches to vaccine development
- rational attenuation: specific modification/deletion f a virus gene that confers virulence eg thymidine kinase deletion in pseudorabies virus
- vector-mediated sub-unit delivery: rabies glycoprotein gene into vaccina virus for foxes
- virus-like particles: eg HPV 16 and 18 vaccine is made of only capsid, with no genome
- nucleic acid immunisation: prime-boost. Inject DNA encoding the desired antigen under a strong promoter. Boost with a live virus vector expressing the same antigen.
what is the main challenge with antiviral chemotherapy? How is this dealt with?
- Specificity: viral things not human
- target nucleic acid polymerases, proteases, influenza NA, HIV integrase
- made into dNTP form by cellular kinases
- incorporated into DNA by reverse transcriptase
- chain terminator (no 3' hydroxyl)
- made into dNTP by HSV thymidine kinase
- chain terminator
4 types of antiviral chemotherapy
- protease inhibitors (for cleaving gag and pol of HIV
- Tamiflu (Oseltamivir phosphate): analogue of sialic acid, inhibits NA. Agglutination happens.
4 useful things about viruses
- studying cell biology and immunology
- gene therapy
- vaccine development
- cancer therapy (oncolytic viruses)