Lecture 26. Prevention and Control -- Vaccines
Flint et al., chapter 19, pp. 703 - 725
How do we acquire immunity?
Passive Immunity in Infants
Artificial Passive Immunity
• Gamma globulin – Ig’s from pooled blood of at least 1,000
human donors• variable content• non-specific
• Specific immune globulin (SIG)– higher titers of specific antibodies
• Antisera and antitoxins of animal origin
Antibody and effector T-cells are the basis of protective immunity
•Primary infection stimulates an initial immune response.
•A second infection is “inapparant” because it provokes no symptoms.
•However, it does re-stimulate and fine tune the immune response.
•Years later, memory B- and T-cells can become reactivated upon infection, protecting the individual from disease
Artificial Active Immunity
• Vaccination (Immunization)– exposing a person to material that is antigen
but NOT pathogenic.
History of Vaccination: Smallpox
• Smallpox killed or maimed 10% of humankind. • Killed > 300,000,000 people in the 20th century alone• Ancient Chinese history: a once in a lifetime disease.• 11th century China and India: “Variolation”
– Scratch a healthy person with pus from infected person– If they don’t die, they are immune for life
VaccinationMay 14, 1796, Edward Jenner
• Noted that milkmaids got cowpox, but not smallpox.• Injected pus from a cowpox lesion under the skin of a child• Waited 2 weeks• Deliberately infected the child with smallpox.• The boy survived• (Today, Jenner would be majorly sued, would lose his license,
be put on trial, get a good lawyer, write a book, and do the talk show circuit…Just like Michael Jackson’s doctor!)
History of Vaccination• Despite Jenner’s success, it
took 100 years til the next vaccine.
• 1881, Louis Pasteur: coined the word Vaccine.– Used dried spinal cord from
rabid rabbit to create a rabies vaccine.
– Also developed vaccines to fowl cholera and anthrax
• July 6, 1885: 9 year old Joseph Meister who was badly bitten by a rabid dog.
• Although Pasteur was not a licensed physician and faced legal risks, the boy would most certainly have died without treatment like many before him.
• Pasteur decided to treat the boy nevertheless and inoculated Joseph with rabies vaccine that had been tested only on dogs previously.
• The risk paid off and the boy recovered dramatically.
Large scale vaccination programs
• Dramatic improvements in public health.
• Nobody in this room has had…– Smallpox, Polio, Measles,
Chickenpox– Mumps, Rubella
• …Because of vaccination
• Smallpox is the only human disease to ever be eradicated
Fig. 19.1
Characteristics of a good vaccine
• Safe• Few side effects• Give long lasting, appropriate protection• Low in cost• Stable with long shelf life (no special storage
requirements)• Easy to administer• Inexpensive• Public must see more benefit than risk
Types of vaccines
• whole agent
• subunit– recombinant– individual parts alone
Whole agent vaccines -- Killed using heat or formaldehyde
Inactivated polio vaccine (Salk)
Influenza (Classic)
epitopes
epitopes
Live virus Killed virus
Whole agent vaccines -- Attenuated
• attenuated - a process that lessens the virulence of a microbe
oral polio vaccine (Sabin),
MMR (measles, mumps, rubella)
Influenza -- FlumistTM
Vaccines stimulate immune memory
•Killed virus vaccine requires multiple doses (booster shots) to adequately stimulate a protective immune response
•Live virus vaccines replicate in the host.•No requirement for boosters.
Attenuation of viruses by passage through non-human cells
1. Pathogenic virus isolated from patient, grown in human cells
2. Infect monkey cells with cultured virus
3. Virus acquires many mutations that allow it to grow well in monkey cells
4. Mutations make the virus unable to grow well in human cells
Vaccine candidate 43
1 2
• Advantages for live vaccines– multiply like natural organism– require fewer doses and boosters– long-lasting
• Disadvantages for live vaccines– special storage– back mutation– side effects
Live attenuated Sabin oral poliovirus vaccine
Construction of recombinant attenuated virus
1. Isolate virus2. Clone genome3. Isolate virulence gene4. Mutate or delete virulence
gene5. Resulting virus is
• Viable• Immunogenic• Not virulent• Can be used as a
vaccine
Subunit vaccines
• Single antigen or mixture of antigens
• Safer (cannot reproduce)
• However, often less effective than whole agent vaccines
• Can be costly
• Always require boosters
Overcoming Subunit vaccine problems
1. Multiple doses - booster shots
2. Use adjuvants• prolongs stimulation of immune
response
• works by trapping the antigens in a chemical complex and releases them slowly
Vaccine delivery systems and adjuvants
ISCOMS as peptide delivery systems
Fig. 19.9
Recombinant vaccines
• Genetic engineering approach
• Hepatitis B• Vaccina or
adenovirus alteration
DNA vaccines
• Create a recombinant plasmid containing a gene encoding a specific antigen.
• Engineer in sequences1. Enabling it to be expressed in humans2. Passaged through bacteria
• Introduce it into humans • Let the human cells produce the antigen• Present it to T-cells• Provoke immune response
Representative results of DNA vaccine trials