Current concepts of immunoprophylaxis

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Immunizing agents prevent the occurrence of disease by giving
protection to the host.

There are three ways by which one can prevent infections.

by reducing the exposure to pathogenic microorganisms.

by acquiring immunity to the particular pathogen.

by using antimicrobial agents to prevent colonization and
infection.

Aims of vaccination

Eradication of disease

Observed dramatic down ward trend in the incidence of
diseases against which the vaccines are in use

Protection of individual against infection and block the
transmission

Milestones in immunization

Edward Jenner discovers small pox vaccine
Modern era of the vaccine
1885
Rabies vaccine

1920s
Diphtheria and Tetanus

1934
Pertussis

1955
Salk polio
1960s
Mumps measles and
rubella virus
Sabin polio

1985
Haemophilus

1990s
Hepatitis and
varicella

Different modes of immunity
Natural resistance
Artificial
Natural
Passive
Artificial Natural
Active
Immunity
Acquired
Passive Immunity
Natural

Placental transfer of IgG

Colostral transfer of IgA

Artificial

Antibodies

Immune cells

Advantages and Disadvantages of Passive Immunization
Advantages

Immediate protection
Disadvantages

No long term protection

Serum sickness

Risk of hepatitis and AIDS


Active Immunization
Natural

Exposure to clinical
infection
Artificial

Attenuated organisms

killed organisms

sub-cellular fragments

Toxins

others
How does induction of the immune response occur?

Antigens stimulate the immune system


Memory cells are produced in an immune response,
remains in the blood stream.


Lives for the life span of the host, ready to mount a quick
protective immune response against subsequent infections


This response is often so rapid that infection doesn't
develop
Requirements of a good vaccine
The ideal vaccine should be effective, safe, stable and of low
cost

To be effective a vaccine must not only induce an adequate
immune response, but the response must also be of right type

Tuberculosis cell mediated immunity
Streptococcal pneumonia opsonizing antibody
Mucosal protection against polio IgA
Duration of response

For short term protection primary antibody response
arising from the vaccine is sufficient

No requirement of memory cells

Long term - requirement of memory cells




The safety of vaccines

Stability is particularly critical with living attenuated
vaccines

Attenuated live polio vaccine: stable for 1 year at 4
0
C
but only for a few days at 37
0
C

The cost of a vaccine is relative, but can not be high for
use in developing countries
Methods used to attenuate viruses for vaccine
production.

Use of a related virus from another animal - use of cowpox to
prevent smallpox.

Selection of mutants

Adaptation to low temperature
Virus is encouraged to grow at low temperature; at 25C (polio
and measles virus)

Serial passage in cells cultured in vitro
Polioviruses were passaged in monkey kidney cells.
Virulence can be checked by signs of neurotoxicity in monkey
Live attenuated vaccines : Poliovirus, measles, rubella, mumps,
yellow fever, Mycobacterium bovis, Salmonella typhi

Killed vaccines rabies, influenza, polio (Salk), hepatitis A,
S. typhi, V. cholerae, B. pertussis, Y. pestis
Organism Method of inactivation
Viruses
Rabies
Influenza
Polio (Salk)
Hepatitis A

Beta propiolactone
Beta propiolactone
Formaldehyde
formaldehyde
Bacteria
S.typhi
V. cholerae
B. pertussis
Y pestis

Heat plus phenol or acetone
heat
Heat and formaldehyde
colicin
formaldehyde
Inactivated vaccines
Advantage of live attenuated vaccine
Replication of the virus

Localization to the appropriate part of the body

Efficient induction of cytotoxic T cells

Will spread through the population by normal transmission
route
Disadvantage of live attenuated vaccine
Mutation reversion of virulence

No test to predict whether the reversion occur in the
immunized individual

Should not be given to immunocompromised individual

A second virus can contaminate the vaccines if it were present
in the cell culture- both killed and live vaccines
Advantages of inactivated vaccines

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

Disadvantages of inactivated vaccines

Many vaccinees do not raise immunity
Boosters needed
No local immunity (important)
Higher cost
Shortage of monkeys (polio)
Failure in inactivation & immunization with virulent virus
Characteristic Live vaccine Killed vaccine
Duration of immunity Longer Shorter
Effectiveness of protection Greater Lower
Immunoglobulins produced IgA and IgG IgG
Cell- mediated immunity
produced Yes Weakly or none
Reversion of virulence Possible No
Excretion of vaccine virus
and transmission to
nonimmune contacts Possible No
Adjuvants

Used to potentiate the immune response

Functions to localize and slowly release antigen at or near the site of
administration.

Functions to activate APCs to achieve effective antigen processing or
presentation

Materials that have been used include:-
Aluminum salts
Mineral oils
Calcium phosphate
Mycobacterial products, eg. Freud's adjuvants : toxic to human use
(Muramyl dipeptide found to be less toxic, retain most of the benefits of
mycobacterium)
B. pertussis

Experimental : liposomes, IL-1, IL-2, interferon
Acellular vaccines

Use antigenic part of the disease causing organism - capsule,
the flagella, or part of the protein cell wall

Haemophilus influenzae B (Hib) vaccine.

Acellular vaccines exhibit some similarities to killed vaccines.

Induce the strongest immune responses - require a booster
every few years for their continued effectiveness.

Both killed & acellular vaccines can not cause disease -
considered to be safe for use in immunocompromised
patients.
Toxoid vaccines

The toxin is treated with aluminum or adsorbed onto
aluminum salts to decrease it's harmful effects toxoids

Diphtheria and the tetanus vaccines.

Induce low level immune responses - administered with an
adjuvant

The diphtheria and tetanus vaccines are often combined with
the pertussis vaccine as a DPT immunization.

The pertussis acts as an adjuvant in this vaccine.

Toxoid vaccines often require a booster every ten years
A variety of viruses and bacteria can be used as vectors for
cloned genes - best known expression vector: E.coli

The DNA sequence coding for the foreign gene is inserted into
the plasmid vector along with a vaccinia virus promoter and
vaccinia thymidine kinase sequences.

The resultant recombination vector is then introduced into cells
infected with vaccinia virus to generate a virus that expresses the
foreign gene.

The genes of several viruses can be inserted, so the potential
exists for producing polyvalent live vaccines. HBsAg, rabies,
HSV and other viruses have been expressed in vaccinia
Recombinant vaccines
antibody
Future Vaccines: Anti-idiotype vaccine
epitope
Antibody with epitope binding site
Virus
antibody
Make antibody against
antibody idiotype
Anti-
idiotype
antibody
Anti-idiotype
antibody mimics
the epitope
Anti-anti-idiotype
antibody
Use anti-idiotype antibody as injectable
vaccine
Antibody to anti-idiotype
antibody
Anti-idiotype
antibody
Binds and
neutralizes virus

Anti-anti-idiotype
antibody

Anti-anti-idiotype
antibody
Use as vaccine
DNA Vaccines
The vaccine DNA is injected into the cells of the body, where the
"inner machinery" of the host cells "reads" the DNA and converts it
into pathogenic proteins.

Because these proteins are recognised as foreign, they are processed
by the host cells and displayed on their surface, to alert the immune
system, which then triggers the immune responses .

These vaccines would be extremely safe and devoid of side effects
since the foreign antigens would be directly produced by the host
animal.

In addition, DNA is relatively inexpensive and easier to produce than
conventional vaccines.

The time for development is relatively short which may enable timely
immunization against emerging infectious diseases.
birth Hepatitis B
2-6 months Polio
Diphtheria
Pertussis
Tetanus
Hib
12-18 months Measles
Mumps
Rubella
Varicella
Pneumococcal
10-16 years Tetanus
diphtheria
Over 50 years Infleuenza (>50yrs)
Pneumococcal (>65yrs)
Current vaccine practice in US
Organism Disease
HIV
Hepatitis C
Hepes simplex virus
Cytomegalovirus
Epstein Barr virus
Rhinovirus
Dengue virus
AIDS
hepatitis
genital infection
effect on fetus
glandular fever
common cold
dengue fever
Neisseria gonorrhoeae
M. tuberculosis
M. leprae
T. pallidum
C. trochomatis
gonorrhea
tuberculosis
leprosy
syphilis
trachoma, urethritis
Plasmodium spp
Tryponema spp
Filaria spp
Leishmania spp
Schistosoma spp
malaria
trypanosomiasis
filariasis
leishmaniasis
schistosomiasis
Vaccines still awaited
Further reading
Chapter 34, vaccination, C. Mims, Medical
microbiology, 3
rd
edition