Smallpox and Other Eradication Programs Flashcards
What virus causes smallpox?
Variola virus
- Member of Orthopoxvirus
- Family Poxviridae
What is the normal host of the virus causing smallpox?
Humans
What are poxviruses?
- Large DNA viruses that replicate in the cytoplasm of infected cells
- The large genome contains genes which encode for numerous nonstructural proteins, several of which counteract the immune system
What are common complications of poxviruses?
- Blindness
- Pockmarks (deep pitted scars, most prominent on the face)
What is variolation?
- Developed by practitioners in Asia
- Involved blowing dried smallpox scabs into the nose, the individual contracted a mild form of the disease
- However, 1-2% of the variolated died
How did Edward Jenner introduce vaccination?
- He recognised that cowpox-infected dairy maids were immune to smallpox
- Deliberately used a Lancet and scratched two lines on James Philipp’s (8 years old) arm
What was the mechanism behind Edward Jenner’s procedures in vaccination?
- The use of Lancet attenuated the virus
- The scratching activated the innate immune response so that the deliberate infection was contained within the inoculation site
Describe the smallpox eradication campaign.
1950: Smallpox was eradicated in industrialised nations, but there were still cowpox cases around the world; Vaxinia virus was freeze dried
1967: Vaccination reduced the number of smallpox cases; WHO launched an intensified eradication plan
- Jet injectors were used, which used pressurised air to shoot the virus into the arm
- They were found expensive and ineffective
- Bifurcated needles were then preferred as they were easy to carry in the field and could be sterilised to be reused = Cost effective
Describe the poliovirus.
- A small RNA virus (picornavirus)
- ssRNA; has no envelope (unlike poxviruses), which makes them more difficult to disinfect
What does poliovirus cause?
Impaired breathing
Poliomyelitis
- A viral paralytic disease
- The Poliovirus enters the body orally and infects intestinal wall
- Virus proceeds to the blood stream and CNS, causing muscle weakness and paralysis
Most infected people are asymptomatic or have mild symptoms
What kind of vaccines were used against polio?
Inactivated vaccines and oral (live) vaccines
What was the inactivated polio vaccine (IPV)?
Salk Vaccine
- Formalin-inactivated poliovirus
Give an example of an oral poliovirus vaccine.
Sabin Vaccine
- Poliovirus is passed through nonhuman cells (monkey kidney cells) at a subphysiological temperature
- The virus alters its enzymes to adapt to the subphysiological environment
- When the virus is injected in humans, it is in a weakened (attenuated) form
- However, there is risk for the attenuated virus reverting back to its wild-type form
What is passive immunity?
- Temporary and does not engage immune response or generate memory
- Can be acquired naturally (maternal IgG crosses the placenta to foetus) or delivered artificially
- Protect individuals from subsequent infectious disease or in those who lack humoral responses
What are live attenuated vaccines?
- Microorganisms are attenuated (disabled) so they are unable to cause pathogenicity but still able to slowly and transiently grow within the inoculated host
- Provides active immunity
What are the advantages and disadvantages of live attenuated vaccines?
Advantages:
- Have capacity for slow and transient growth
- Able to replicate within host cells
- Prolongs immune system exposure to immunogens on the attenuated microorganism = Increased immunogenicity and efficient production of highly effective memory cells
- Only require single immunisation = Major advantage in developing countries, where individuals don’t return for boosters
Disadvantages:
- The live forms can sometimes mutate and revert to a more virulent form in the host
What are inactivated (“killed”) vaccines?
- Heat or chemical treatment kills a pathogen so it’s incapable of replication
- Still able to induce an immune response to at least some of the immunogens within the organism
- Provide passive immunity
What are the disadvantages of inactivated vaccines?
- Require repeated boosters to achieve protective immune status
- Do not replicate in the host
- Less effective than attenuated vaccines in inducing cell-mediated immunity
What are recombinant vaccines?
Genes that encode key antigens of virulent pathogens can be introduced into safe attenuated viruses or bacteria that are used as live carriers
The attenuated organism serves as a vector = Replicates within the body and expresses the individual gene product/s from the pathogen
What is the advantage of using recombinant vaccines?
Like live attenuated vaccines, they can prolong immunogens delivery and encourage cell-mediated responses
Reversion potential is virtually eliminated as most of the pathogen’s genome is missing
What is active immunity?
- Triggered by natural infection or artificial exposure to a form of pathogen (vaccine)
- Aims to induce a memory response that will be protective in the future
Compare and contrast active and passive immunity.
Active Immunity
- Mediated by T and B cells = Takes time to develop
- Immunity is long lasting and requires few (if any) boosters
Passive Immunity
- Uses antibodies
- Antibodies are naturally broken down or can disappear when there is an absence of B cells = Works very quickly but short lasting
What are the functions of adjuvants?
- Potentiate the immune response
- Localise and slowly release antigen at or near site of administration
- Activate APCs to achieve effective antigen processing/presentation
What materials have been used as adjuvants?
- Aluminium salts (widely used in humans)
- Mineral salts (used in animals)
- Mycobacterial products (Freud’s adjuvants – now restricted due to severe side effects)
What are DNA vaccines?
- Based on plasmid DNA encoding antigenic proteins
- Plasmid DNA is injected directly into the recipient’s muscle
- Host cells take up the DNA and produce immunogenic protein in vivo
- Antigen is expressed by MHC Class I molecules = Activates better responses by memory T and B cells, CTLs, and plasma cells
What are the different types of vaccines?
- Inactivated vaccines
- Live attenuated vaccines
- Recombinant vector vaccines
- Conjugated vaccines
- DNA vaccines
Give 3 common vaccines for human diseases.
Polio (Sabin vaccine) – Live attenuated
- Advantage: Strong immune response; lifelong immunity with few doses
- Disadvantage: Requires refrigerated storage; may mutate to virulent form
Hepatitis B – Subunit
- Advantage: Specific antigens lower the chance of adverse reactions
- Disadvantage: Difficult to develop
Polio (Salk vaccine) or Cholera – Inactivated
- Advantage: Stable; safer than live vaccines; refrigerated storage not required
- Disadvantage: Weaker immune response than live vaccines; booster shots required