History of vaccinationHistory of vaccination

Variolation – X–XVIII century:

– immunizing patients against smallpox by infecting them with substance from the pustules of patients with a mild form of the disease

Istorijat vakcinaIstorijat vakcina

First vaccination: Edward Jenner- in 1796. vaccinated

a boy James Phipps with material from the cowpox blisters of the

hand of a milkmaid Sarah Nelmes

History of vaccinationHistory of vaccination

Richard Dunning – 1803.introduced the term “vaccination”

“vacca” – lat. cow

“vaccinia” – laboratory strain of cowpox virus

History of vaccinationHistory of vaccination

Louis Pasteur – XIX century:rabies vaccine

First vaccination against rabies – in 1885. :A boy Joseph Meister after being bitten by a rabid dog

The Aims of The Aims of ImmunizationImmunization

to prevent infectionto modify the course of disease

Time of immunization:before exposure to wild type virusafter exposure (and before onset of symptoms)

Characteristics of a good vaccineCharacteristics of a good vaccineAbility to produce effective immune response

Long-term protection (ideally life-long)

Safe application

Stable in transport

Low cost

Immunity in vaccinated Immunity in vaccinated peoplepeople

Immunity in viral infection is dependant on immune response to viral antigens.

Immune response should:Eliminate free viral particlesDestroy virus-infected cells

Immunity in vaccinated peopleImmunity in vaccinated people

Surface viral antigens (protective antigens) - induce production of neutralizing antibodies

Inner viral antigens (structural and non-structural) - induce cellular immunity

TYPES OF VIRAL VACCINESTYPES OF VIRAL VACCINES

TYPES OF VIRAL VACCINESTYPES OF VIRAL VACCINES

DNA vaccinesDNA vaccines

Live attenuated vaccinesLive attenuated vaccines

Attenuated viral strains –Obtained by continuous passage of the virus through a foreign host

Attenuated mutants - immunogenic but not virulent

Live attenuated vaccinesLive attenuated vaccines

Prednosti:Activate humoral and cellular immune response

Administration is simulating natural route of infection (stimulates local IgA immunity)

Stimulate production of interferon

Durable immunity

Live attenuated vaccinesLive attenuated vaccines

Nedostaci:Reversion to virulenceLow level of residual virulenceReactivation with another live virus inside hostCannot be applied in pregnancy and in immunocompromised patientsUnstable on room temperature(require +40C – cold chain)

Live virulent vaccinesLive virulent vaccines

Similar antigens in related viruses are responsible for cross-immunity.

Examples:v. vacciniae and v. variolaeSimian and human rotavirusBovine and human v. parainfluenzae type 3

Insertion of viral gene in the genome of avirulent virus = live vaccine.

Recombinant virus replicates in vivo and produces protective antigens.

Live recombinant vaccinesLive recombinant vaccines

Live recombinant vaccinesLive recombinant vaccines

Viral geneExamples: HBV, HSV, influenza, rabies

Most often used vector:v. vacciniae

Side effects: progressive vaccinia, eczema vaccinatum, encephalitis)

Inactivated killed vaccinesInactivated killed vaccines

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Are produced by : physical (heating, UV) or chemical (formaldehydeand b propiolactone) procedures that destroy infectivity but preserve immunogenicity.

Inactivated killed Inactivated killed vaccinesvaccines

Disadvantages:Stimulate production of antibodies in lower titreInduce weaker cellular immune responseDo not induce local immunity (IgA)Short-lived immunity (booster doses needed)Higher cost

Subunit vaccinesSubunit vaccinesPurifiedPurified

Viral immunogenicity is not dependant on the presence of nucleic acid.

Subunit vaccines contain purified and concentrated envelope or capsid antigens.

Advantage:Safe (except for rare local reactions)

Disadvantage:Weaker immunogenicity (adjuvant required)Do not induce cellular immune response

Subunit vaccinesSubunit vaccinesPurifiedPurified

Subunit vaccinesSubunit vaccinesSyntheticSynthetic

Synthetic peptides with the same amino acid sequence as viral antigens

Subunit vaccinesSubunit vaccines““ClonedCloned”” by recombinant DNA by recombinant DNA

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These vaccines are produced by incorporation of viral gene (for protective antigen) in another microorganism – E. coli or yeasts. Microorganism will produce large amounts of viral antigen.

Viral antigen is then purified from culture and used as vaccine.

DNA vaccinesDNA vaccines

Insertion of a gene for viral protective antigen in bacterial plasmid

Plasmid does not replicate in vivo but protective antigen is transcribed

Viral vaccines in Viral vaccines in practicepractice

Polio viruscontains all 3 viral types

Two types of vaccine: Salk– inactivated killed (Sweden, Finland, Netherlands, Iceland)Sabin– live attenuated(oral application)

Viral vaccines in practiceViral vaccines in practice

MMR:Morbilli, Mumps, Rubella

Live attenuated vaccine

Viral vaccines in practiceViral vaccines in practice

Influenza

Inactivated killedNew vaccine every yearbased on WHO data(contains strains presentin the population in thegiven season)

Viral vaccines in practiceViral vaccines in practiceKilled (whole virion)

Split

Subunit(surface antigens)

Live attenuated

Influenza

Viral vaccines in practiceViral vaccines in practiceRabiesLive attenuated and inactivated killed

Applied as:Pre-exposure protection –3 doses, occasional “booster”dose (veterinarians, laboratory personnel, farmers)Post-exposure protection –5-6 i.m. injections starting from day 0

Viral vaccines in practiceViral vaccines in practice

Hepatitis B

subunit – HBsAgrecombinant

(doctors, surgeons, laboratory workers, dentists)

Children of Children of HBsAgHBsAg+ mothers+ mothers

Viral vaccines in practiceViral vaccines in practice

Hepatitis A

Inactivated killed

2 doses

Travelers in endemic regions

Viral vaccines in practiceViral vaccines in practice

Varicella-zoster

Live attenuatedImmunocompromisedchildren

Viral vaccines in practiceViral vaccines in practice

Rotavirus

live attenuated vaccine

Viral vaccines in practiceViral vaccines in practice

Yellow fever

Live attenuated

People living in endemic areas, travelers to endemic areas

1 dose and “booster”every 10 years

HPV“Cloned” by recombinant DNA

technique(VRL- viral like particle)

1. Duovalent (types 16 i 18)2. Quadrivalent (types 6, 11, 16 i 18)

Viral vaccines in Viral vaccines in practicepractice

Eradication of Eradication of Small poxSmall pox

Last case of small pox in the world – Somalia 1977.