(Vector vaccines)
BY
Maneesh kumar.M
Attenuated vaccines are derived from wild
or disease causing viruses or bacteria that
have been weekend under laboratory
conditions. Attenuated vaccine is strong
enough to cause immune response, but too
weak to cause disease.
 Natural viruses need to produce thousands of
times during infection to cause disease. These
weekend viruses are only able to reproduce
fewer than twenty times.
 With such little production, attenuated
viruses are not able to create nearly enough
copies of themselves to cause disease.
 However, enough viral particles are created
to create memory antibodies and keep the
body from getting the viral infection should it
enter the body naturally in the future.
Preparation of live but weaken pathogens
occur in two ways:
Step1:use the tissue culture to grow new
viruses.
Step2:Fill the syringe with a strain of the
virus that has desirable chracteristics.
A live vector vaccine is a vaccine tat causes
a chemically weakened virus to transport
pieces of the pathogen in order to
stimulate an immune response .The genes
used in this vaccines are usually antigen
coding surface proteins from the
pathogenic organism.
Cholera is an infection of the small
intestine caused by some strains of the
bacterium vibrio cholerae. The classical
symptom is large amount of watery
diarrhoea.
Two types of vaccines are available
 A vaccine consisting of killed whole – cell
v.cholerae 01 in combination with a
recombinant B-sub unit of cholera toxin is
available since early 1990’s. Work out is
50-60 % for 3 years.
 Since 1994, another oral vaccine is the live
attenuated CVD 130-HgR vaccine containing
the genetically manipulated classical
v.cholerae strain CVD 103-HgR. Work out is
80%.
 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.
Antigen Gene
Virus
Patient
Antigen Protein is Made
• 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.
 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.
Picture representing the formation of malaria
vaccine by using a 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
 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.
• 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.
 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.
DISADVANTAGES
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
vector vaccines
vector vaccines

vector vaccines

  • 1.
  • 2.
    Attenuated vaccines arederived from wild or disease causing viruses or bacteria that have been weekend under laboratory conditions. Attenuated vaccine is strong enough to cause immune response, but too weak to cause disease.
  • 3.
     Natural virusesneed to produce thousands of times during infection to cause disease. These weekend viruses are only able to reproduce fewer than twenty times.  With such little production, attenuated viruses are not able to create nearly enough copies of themselves to cause disease.  However, enough viral particles are created to create memory antibodies and keep the body from getting the viral infection should it enter the body naturally in the future.
  • 4.
    Preparation of livebut weaken pathogens occur in two ways: Step1:use the tissue culture to grow new viruses. Step2:Fill the syringe with a strain of the virus that has desirable chracteristics.
  • 5.
    A live vectorvaccine is a vaccine tat causes a chemically weakened virus to transport pieces of the pathogen in order to stimulate an immune response .The genes used in this vaccines are usually antigen coding surface proteins from the pathogenic organism.
  • 6.
    Cholera is aninfection of the small intestine caused by some strains of the bacterium vibrio cholerae. The classical symptom is large amount of watery diarrhoea.
  • 7.
    Two types ofvaccines are available  A vaccine consisting of killed whole – cell v.cholerae 01 in combination with a recombinant B-sub unit of cholera toxin is available since early 1990’s. Work out is 50-60 % for 3 years.  Since 1994, another oral vaccine is the live attenuated CVD 130-HgR vaccine containing the genetically manipulated classical v.cholerae strain CVD 103-HgR. Work out is 80%.
  • 9.
     Poxviruses havebeen 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.
  • 10.
  • 11.
    • Recombinant livevector 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.
  • 12.
     Homologous vector: Whenthe 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.
  • 13.
    Picture representing theformation of malaria vaccine by using a vector
  • 14.
    ADVANTAGES: •Infects human cellsbut 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
  • 16.
     The genethat 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.
  • 17.
    • Salmonella infectscells 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.
  • 18.
     Since thegenes 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. DISADVANTAGES
  • 19.
    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