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The conventional approach to vaccine

development uses the following methods


Live(attenuated)vaccines
Killed(inactivated vaccines)
Subunit vaccines

Schematic representation of the conventional approach


to bacterial vaccine development (following Pasteurs
principles).

Not

all pathogens can be grown in


culture.
Some cell-associated bacteria
require specific cell cultures for
growth, and this is expensive.
Extensive safety procedures for
personnel and the environment may
be required to prevent exposure to
pathogenic bacteria.

Insufficient

killing or attenuation may


result in the introduction of virulent
organisms into the final vaccine, and
inadvertently cause disease.
The products may be rather ill-defined
and variable and
The conventional approach to developing
attenuated (but not killed) vaccines is
time consuming, and can take decades.

Reverse

vaccinology is an improvement on
Vaccinology, pioneered by Rino Rappuoli and
first used against meningococcus. Since then,
it has been used on several other organisms.
The basic idea behind Reverse Vaccinology is
that an entire pathogenic genome can be
screened using bioinformatics approaches to
find genes.
Next, those genes are filtered for desirable
attributes that would make good vaccine
targets such as outer membrane proteins.
Those proteins then undergo normal wet lab
testing for immune responses.

Reverse

vaccinology (RV) means to identify


and characterise the antigen using
bioinformatics.
In RV, you start from the genome and not
from the pathogen itself i.e. you start from
the opposite direction, thats why it is called
reverse.

Approaches used in the genome era to identify vaccine


candidates

Advantages

Fast access to virtually every antigen


Non-cultivable can be approached
Non abundant antigens can be identified
Antigens not expressed in vitro can be identified.
Non-structural proteins can be used

Disadvantages

Non proteinaceous antigens like polysaccharides,


glycolipids cannot be used.

Group

B meningococcus
Malaria
Tuberculosis
Syphilis
Hepatitis C virus
Other pathogens
Chlamydia
Pneumococcal
Streptococcus
Pseudomonas
Borrelia
Escherichia coli.

The principle of reverse vaccinology, using


Neisseria meningitidis as an example.

Microbial genomes and vaccine design: refinements to the

classical reverse vaccinology approach by Marirosa Mora,


Claudio Donati, Duccio Medini, Antonello Covacci and Rino
Rappuoli.,2006.
New ways to identify novel bacterial antigens for vaccine
development Abdolreza (Reza) Movahedi, David J.
Hampson.,2008.
Reverse vaccinology by Rino Rappuoli.,2000.
Vaccinology at the beginning of the 21st century by Andreas
Wack and Rino Rappuoli.,2005.