VACCINES

DEFINITION A vaccine is biological preparation that improves immunity to a particular disease, a vaccine typically contains a disease causing micro-organisms often weakened or killed.

No vaccine is 100% effective! Most that are used in North America are between 70 and 95% effective

Vaccines provide both Individual benefit and a Public health benefit.

“herd immunity”

History

• Mummies

• China/India Crusaders

• W Europe: fatality rate 25%

• History changed:

Cortes

Louis XIV

• 1% v. 25% mortality

• Life-long immunity: No drift or shift (proof

reading)

• UK: 1700’s

• China: 1950

• Pakistan/Afghanistan/Ethi

opia 1970

Variolation

Small pox

Vaccination

• Jenner 1796 : Cowpox/Swinepox

• 1800’s Compulsory childhood vaccination

• 1930’s Last natural UK case

• 1940’s last natural US case

• 1958 WHO program

• October 1977: Last case (Somalia)

Reasons for success of smallpox vaccination

No animal reservoir Lifelong immunity

Rare Subclinical cases

Infectivity does not precede overt symptoms

One Variola serotype

Effective vaccine

Major commitment by governments

Estimated Herd Immunity thresholds for vaccine preventable diseases

Disease Transmission R0[N] Herd immunity threshold

Diphtheria Saliva 6-7 85% Measles Airborne 12-18 83 - 94% Mumps Airborne droplet 4-7 75 - 86% Pertussis Airborne droplet 12-17 92 - 94% Polio Fecal-oral route 5-7 80 - 86% Rubella Airborne droplet 5-7 80 - 85% Smallpox Social contact 6-7 83 - 85%

^  - R0 is the basic reproduction number, or the average number of secondary infectious cases that are produced by a single index case in completely susceptible population.

TWO FORMS OF VACCINES

PROPHYLACTIC THERAPEUTIC

Prevent future infection by any means. e.g. to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen).

Prevent severity of infection problems already occurred. e.g. vaccines against cancer are also being investigated.

ingredients

Preparation of vaccine

Separate two effects of organism

Formalin can be used

Use antigen part of virus

Attenuate virus aging altering or mutating

Toxins of toxoid vaccines are treated with

aluminum

Vaccine Type Disease

Live, attenuated vaccine

Measles, mumps, rubella, polio (Sabin vaccine), yellow fever

Inactivated or “killed” vaccine

Cholera, flu, hepatitis A, Japanese encephalitis, plague, polio (Salk vaccine), rabies

Toxoid vaccine Diphtheria, tetanus

Subunit vaccines Hepatitis B, pertussis, pneumonia caused by Streptococcus pneumoniae

Conjugate vaccines

Haemophilus Influenza type B, pneumonia caused by Streptococcus pneumoniae

DNA vaccines In clinical testing

Recombinant vector vaccines

In clinical testing

INACTIVATED OR KILLED VACCINE

Advantages of inactivated vaccine Gives sufficient humoral immunity if boosters given No mutation or reversion Can be used with immuno- deficient patients

Disadvantages of inactivated vaccines Boosters needed Many of them donot raise immunity Higher cost

Attenuation

ATTENUATION is usually achieved by passage of the virus in

foreign host such as embryonated eggs or tissue culture cells.

These tend to be less virulent for the original host. In Sabin

polio vaccine, attenuation was only achieved with use of high

inocula and rapid passage in primary monkey kidney cells.

The viruses became overgrown with a less virulent strain (for

humans) that could grow well in non- nervous tissue but not

in CNS. Non-virulent strains of all three polio types produced

for the vaccine.

LIVE ATTENUATED VACCINE

Advantages of Attenuated Vaccine 1)Activates all phases of immune system. Can get humoral IgG and local IgA 2)Raises immune response to all protective antigens . Inactivation may alter antigenicity. 3)More durable immunity; more cross-reactive

Disadvantages of Attenuated vaccine 1) Mutation; reversion to virulence 2) Spread vaccine not standardized--may be

mutated 3) Problem in immunodeficiency disease

CONJUGATE VACCINE

Polysaccharide coat

Bacterium

toxoid

Currently, conjugate vaccines are available to protect against a type of bacterial meningitis caused by Haemophilus influenzae type b (Hib). Meningitis, an inflammation of the fluid-filled membranes that protect the brain and spinal cord, can be fatal, or it can cause severe, life-long disabilities such as deafness and mental retardation.

DNA VACCINES

The deliberate introduction of a DNA plasmid carrying a protein-coding gene that transfects

Cells in vivo at very low efficiency and expresses an antigen that causes an immune response.

These are often called DNA vaccines but would better be called DNA-mediated or DNA-based

Advantages of DNA vaccines

1) Plasmids are easily manufactured in large amounts

2) DNA is very stable 3) DNA resists temperature extremes

so storage and transport are straight forward

4) DNA sequence can be changed easily in the laboratory. This means that we can respond to changes in the infectious agent

Possible Problems

1) Potential integration of plasmid into host genome leading to insertional mutagenesis

2) Induction of autoimmune responses (e.g. pathogenic anti-DNA antibodies)

3) Induction of immunologic tolerance (e.g. where the expression of the antigen in the host may lead tospecific non-responsiveness to that antigen)