This document presents information on vector vaccines. It defines vector vaccines as using live, attenuated microorganisms like viruses or bacteria that have been genetically modified to express antigens from pathogenic organisms. This allows the vector to act as an antigen delivery system, stimulating an immune response against the pathogen. Common viral vectors discussed are vaccinia virus and adenovirus, while bacterial vectors include attenuated Salmonella. The document outlines the process of producing a vaccinia vector vaccine and discusses advantages like strong immunogenicity and ability to induce different types of immune responses. However, it also notes disadvantages such as high production costs and safety concerns in immunocompromised individuals.

1. PRESENTED BY: Deepti Singh
Ph.D. Biotechnology
FIRST SEMESTER
ENROL. NO. B-1384/14
COLLEGE OF BIOTECHNOLOGY
DUVASU, MATHURA

2. INTRODUCTION
 Vaccines where a live micro-organism (bacteria or virus)
has been modified to express entire genomes or a portion of
foreign RNA or DNA sequences or proteins and where the
replicative competent vector acts as a carrier and may itself
act as a protective immunogen.
 Vector/ Recipient:
A replicative competent micro-organism ( bacteria or virus)
into which the genetic sequence of interest will be inserted.

3. DEFINITION
 Vector vaccines:
Vector vaccines are liquid or freeze-dried preparations of one or
more types of live micro-organisms (bacteria or viruses) that
are non-pathogenic or have a low pathogenicity for the target
species and in which have been inserted one or more genes
encoding antigens that stimulate an immune response
protective against other micro-organisms
 A live vector vaccine is a vaccine that uses a chemically
weakened virus to transport pieces of the virus in order to
stimulate an immune response.
 The genes used in this vaccine are usually antigen coding
surface proteins from the pathogenic organism. They are then
inserted into the genome of a non pathogenic organism such
as Adenovirus were they are expressed on the cells surface
and can elicit an immune response.

4. EXTENSIVELY USED VECTORS
 Poxviruses have been extensively studied as potential
vaccine vectors.
 Vaccinia virus, used as a vector in many vaccines,
induces strong immuno stimulation at the injection site.
Its large genome can integrate many transducible genes
and it has an excellent safety profile.
 Vaccinia has been administered to more than a billion
people since the WHO's 1967 launch of the Global
Smallpox Eradication Program.

5. VECTOR VACCINES: VIRUS AS
ANTIGEN GENE DELIVERY SYSTEM
Antigen Gene
Virus
Patient
Antigen Protein is Made

6. Diagram representing the formation of vector vaccine

7. VACCINIA VECTOR VACCINES
Vaccinia is a good candidate for a live recombinant viral
vaccine because it is:
•benign virus
•replicate in cytoplasm (viral replication genes)
•easy to store

8. RECOMBINANT LIVE VECTOR
VACCINES
• Recombinant live vector vaccines are preparations of one or
more types of live bacteria or viruses.
• One or more DNA/RNA sequences have been inserted into
these organisms.
• These organisms generally have a stable non or low
pathogenic phenotype for the species the vaccine is intended
for.
• Recombinant live vector vaccines are expected to be
attenuated and genetically defined live vaccines, which have
defined, non-reverting mutations or deletions.

9. TYPES OF VECTOR
 Homologous vector:
When the target species of the vaccine is a natural host for
the vector, this is considered a homologous vector.
 Heterologous vector:
When the target species of the vaccine is not one of the
natural hosts for the vector, the vector is classified as a
heterologous vector.

10. Picture representing the formation of malaria vaccine by using a
vector

11. BACTERIAL ANTIGEN DELIVERY
SYSTEMS: BACTERIAL VECTORS
Antigen Gene
Bacterium
Antigen Proteins made on Bacterial cell
Vaccinate Patient

12. BACTERIAL ANTIGEN
DELIVERY SYSTEMS
•Use live non pathogenic bacterium which contains antigen
•Insert antigen gene into flagellin gene
•Epitope is expressed on the flagellum surface
***Flagellin-engineered bacteria is VACCINE**
Advantage - Oral Administration

13. VIRAL VECTOR
ADVANTAGES:
•Infects human cells but some do not replicate
•Better presentation of antigen
•Generate T cell response
DRAWBACKS:
•Can cause bad reactions
•Can be problems with pre-exisiting immunity to virus
•Often can only accommodate one or two antigens

14. PROCEDURE FOR VACCINE
PREPARATION
Genes that encode major antigens of especially virulent pathogens
can be introduced into attenuated viruses or bacteria.
The attenuated organism serves as a vector, replicating within the
host and expressing the gene product of the pathogen.
A number of organisms have been used for vector vaccines,
including vaccinia virus, the canarypox virus, attenuated
poliovirus, adenoviruses, attenuated strains of Salmonella, the
BCG strain of Mycobacterium bovis, and certain strains of
streptococcus that normally exist in the oral cavity.

15. Vaccinia virus, the attenuated vaccine used to eradicate smallpox,
has been widely employed as a vector vaccine.
This large, complex virus, with a genome of about 200 genes, can
be engineered to carry several dozen foreign genes without
impairing its capacity to infect host cells and replicate.
The procedure for producing a vaccinia vector that carries a foreign
gene from a pathogen is outlined as follows:

17. PRODUCTION OF VACCINIA
VECTOR VACCINE
 The gene that encodes the desired antigen (orange) is inserted into a
plasmid vector adjacent to a vaccinia promoter (pink) and flanked
on either side by the vaccinia thymidine kinase (TK) gene (green).
 When tissue culture cells are incubated simultaneously with
vaccinia virus and the recombinant plasmid, the antigen gene and
promoter are inserted into the vaccinia virus genome by
homologous recombination at the site of the nonessential TK gene,
resulting in a TK recombinant virus.
 Cells containing the recombinant vaccinia virus are selected by
addition of bromodeoxyuridine (BUdr), which kills TK cells.

18. ADVANTAGES OF VECTOR
VACCINE
• The genetically engineered vaccinia expresses high levels
of the inserted gene product, which can then serve as a
potent immunogen in an inoculated host.
• Like the smallpox vaccine, genetically engineered vaccinia
vector vaccines can be administered simply by scratching
the skin, causing a localized infection in host cells.
• If the foreign gene product expressed by the vaccinia is a
viral envelope protein, it is inserted into the membrane of
the infected host cell, inducing development of cell-
mediated immunity as well as antibody-mediated
immunity.

19. ADVANTAGES OF VECTOR
VACCINE
• Other attenuated-vector vaccines may prove to be safer than
the vaccinia vaccine. The canarypox virus has recently been
tried as a vector vaccine. Like its relative vaccinia, the
canarypox virus is la genes.
• Unlike vaccinia, the canarypox virus does not appear to be
virulent even in individuals with severe immune suppression.
Another possible vector is an attenuated strain of Salmonella
typhimurium, which has been engineered with genes rge and
easily engineered to carry multiple from the bacterium that
causes cholera.

20. ADVANTAGES OF VECTOR
VACCINE
• Salmonella infects cells of the mucosal lining of the gut
and therefore will induce secretory IgA production.
• Effective immunity against a number of diseases, including
cholera and gonorrhea, depends on increased production of
secretory IgA at mucous membrane surfaces.
• Similar strategies using bacteria that are a normal part of
oral flora are in development.
• The strategy would involve introduction of genes encoding
antigens from pathogenic organisms into bacterial strains
that inhabit the oral cavity or respiratory tract.
• Eliciting immunity at the mucosal surface could provide
excellent protection at the portal used by the pathogen.

21. DISADVANTAGES OF VECTOR
VACCINE
 Since the genes for the desired antigens must be located,
cloned, and expressed efficiently in the new vector, the
cost of production is high.
 When engineered vaccinia virus is used to vaccinate, care
must be taken to spare immuno deficient individuals.

22. STILL A SIGNIFICANT NEED
FOR NEW VACCINES
For other diseases: TB
MALARIA
HIV
1. Increase safety of present
vaccine, lower cost, and
dissemination
2. Road to vaccine development is
long and laden with:
Side effects
Exacerbations of disease state
Acquisition of disease state