Attenuated vaccines

Attenuated vaccines(Vector vaccines)

BYManeesh kumar.M

ATTENUATED VACCINESAttenuated 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.

How it is made ?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.

Vector vaccinesA 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.

choleraCholera 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.

vaccinationTwo 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 1990s. 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%.

Vector vaccines

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.

VECTOR VACCINES: VIRUS AS ANTIGEN GENE DELIVERY SYSTEMAntigen GeneVirusPatientAntigen Protein is Made

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.

TYPES OF VECTORHomologous 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

VIRAL VECTORADVANTAGES:Infects human cells but some do not replicateBetter presentation of antigenGenerate T cell response

DRAWBACKS:Can cause bad reactionsCan be problems with pre-exisiting immunity to virusOften can only accommodate one or two antigens

PRODUCTION OF VACCINIA VECTOR VACCINEThe 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.

ADVANTAGES OF VECTOR VACCINESalmonella 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

STILL A SIGNIFICANT NEED FOR NEW VACCINES

For other diseases: TB MALARIA HIVIncrease safety of present vaccine, lower cost, and disseminationRoad to vaccine development is long and laden with:Side effectsExacerbations of disease stateAcquisition of disease state