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