Vaccines

H.Sidra Yasin (BIOT 412)

Learning objectivesLearning objectives

What are the Methods to produce the vaccines

How we can modify the VaccinesWhat are the Routs of administration of

vaccinesWhat are the Types of vaccines

What is Reverse vaccinology and its purpose

Summary of all topics with conclusion

General Method to produce the General Method to produce the vaccinevaccine

Immunisation Department, Centre for Infections

Vaccine compositionVaccine compositionFollowing are:

Component Purpose Example

Adjuvants enhance the immune response to a vaccine

aluminium salts

Preservatives prevent bacterial or fungal contamination of vaccine

thiomersal

Additives stabilise vaccines from adverse conditions such as freeze-drying or heat, thereby maintaining a vaccine’s potency

gelatine

Residuals from manufacturing process

Inactivating agents

Antibiotics - prevent bacterial contamination during manufacturing process

Egg proteins- some vaccine viruses are grown in chick embryo cells

Yeast proteins

formaldehyde

neomycin, streptomycin, polymyxin B

influenza, yellow fever

HepB vaccine

Modifiers of vaccinesModifiers of vaccines

Modifiers of vaccinesModifiers of vaccines

AdjuvantsBoosters

AdjuvantsAdjuvants

Chemical substance that can be added to a vaccine in order to enhance the immune response to the vaccine.

TypesTypes

1. Freund’s Adjuvant

2. Aluminum Hydroxide3. Aluminum Phosphate (Alum)

BoostersBoosters

Periodic “booster” administration must be given in order to strengthen and lengthen the duration of immunity

Routs of administrationRouts of administration

RoutesRoutes Intradermal administration.

◦ Three types are; intravenous

intramuscular subcutaneous.

Oral administration.◦ Vaccine is usually given in

liquid form.◦ Foods

Intranasal administration.

Types of vaccinesTypes of vaccines

Types of vaccinesTypes of vaccines

Traditional Recombinant vaccines

1. TypesA. InactivatedB. Live C. Attenuated

2. Pathogens A. Bacteria B. Virus C. Parasites

1. Subunit Vaccines2. peptide vaccines3. Attenuated Vaccines4. Vector Vaccines5. Bacterial Antigen

Delivery Systems

Traditional vaccinesTraditional vaccines

Live, Attenuated VccinesLive, Attenuated Vccines

Act like natural infection Live, but weakened, viruses or bacteria Altered organisms, either genetically or

chemically but non pathogenic Example: Attenuated virus vaccine for yellow fever,

which utilizes the YF17D strain, a weakened form of the wild virus.

Live, Attenuated vaccinesLive, Attenuated vaccines

Advantages Disadvantages

• Single dose sufficient to induce long-lasting immunity

• Strong immune response • Local and systemic immunity • Others…Polio and Adeno

• Potential to revert to virulence• Contraindicated in

immunosuppressed patients• Interference by viruses or

vaccines and passive antibody

• Poor stability• Potential for contamination

Inactivated VaccinesInactivated VaccinesEither: Suspensions of whole intact killed

organisms ◦ e.g. whole cell Pertussis, Influenza, Rabies, HepA

Or: Acellular and sub-unit vaccines

◦ e.g. Acellular Pertussis vaccine contains between 2-5 components of the whole cell Pertussis bacteria

Inactivated vaccinesInactivated vaccines

1.whole 1.whole actual pathogen killed, either by a heat treatment or chemically Salk vaccine for polio, which utilizes whole

polioviruses that have been inactivated by formaldehyde.

2.Fractional2.Fractional

Protein based; ToxoidsProtein based; Toxoids Stimulates the antibody mediated response Exotoxins Toxoids are vaccines which consist of exotoxins Immunity against the toxins, but not necessarily the bacteria that produce

the toxins. Examples: Botulinum antitoxen Diphtheria antitoxen Pertusis Tetanus toxoids

Protein based; SubunitProtein based; Subunit Pathogenic agent Use components of pathogenic organism instead of whole

organism Advantage: no extraneous pathogenic particles i.e DNA Disadvantage: Costly Exampleso HSVMethod of productiono Tuberculosiso Foot -and-Mouth Disease virus (FMDV)

Polysaccharide based; purePolysaccharide based; pure

pure cell wall polysaccharide from bacteria

Polysaccharide based; conjugatePolysaccharide based; conjugate

Polysaccharide linked to a carrier protein More potent lacks long term immunological memory

Protect against: o Hibo Pneumococcal diseaseso Tetanuso Diphtheria

Inactivated vaccinesInactivated vaccines

Advantages Disadvantages

• Stable • Constituents clearly defined• Gives sufficient humoral

immunity if boosters given• No mutation or reversion• Can be used with immuno-

deficient patients

• Many vaccinees do not raise immunity

• Shorter lasting immunity • Boosters needed• Need several doses• Adjuvant needed• Failure in inactivation and

immunization with virulent viruses

• Others…

Possible Limitations of Traditional Vaccine Possible Limitations of Traditional Vaccine ProductionProduction

Not all infectious agents can be grown in culture

Animal/human cell culture expensive if needed

Yield of viruses from cultures can be low

Safety precautions for culture of live agents

Insufficient killing/attenuation of agents

Reversion of attenuated agents

Traditional vaccines are less diverse

New StrategiesNew Strategies

Delete virulence genes Use live nonpathogenic carriers for immunization

(unrelated pathogenic agent) Clone antigenic determinants into alternative host Address autoimmune system response/problems

So!!!So!!!

Recombinant vaccinesRecombinant vaccines

TypesTypes

1. Subunit Vaccines2. Peptide vaccines3. DNA Vaccines4. Vector Vaccines

Peptide vaccinesPeptide vaccines

Use discrete portion (domain) of a surface protein as Vaccine.

These domains are ‘epitopes’ antigenic determinants are recognized by antibodies

Use highly immunogenic carrier molecule

With carrier proteinsWith carrier proteins

DNA VaccinesDNA Vaccines DNA vaccines consist of plasmids that contains genes for

certain types of antigens. Once administered, the plasmid is taken up by the target

cell and the genes are expressed. The cell then either excretes the antigen or displays it on

an MHC-I molecule.

Genetic ImmunizationGenetic ImmunizationDelivery of a gene for the antigen to a host organism

• Use vector containing cDNA from viral protein/eukaryotic promoter

• Inject into muscle

POTENTIAL• Eliminates purification of antigen• Protein is modified post-translationally

Chimeric VaccinesChimeric Vaccines Consist of attenuated viruses have been engineered to

carry antigens from multiple types of pathogens. The yellow fever vaccine has been engineered to carry

antigens from HIV, different types of bacteria, malaria, even cancer.

immunity against several different diseases with one administration.

Human Diseases for Which Recombinant Vaccines Are Human Diseases for Which Recombinant Vaccines Are Currently Being DevelopedCurrently Being Developed

Vaccine Production methodsVaccine Production methods

Vaccine Production MethodsVaccine Production Methods

Manufacturing strategies:◦In-vivo◦In-vitro◦Chemical Synthesis

Some vaccines can be produced using any one of the three methods while for other vaccines, only one method will work.

In-VitroIn-Vitro Here, using recombinant

DNA technology, vaccines can be produced in yeast cultures, bacterial cultures, or cell cultures.

Recombinant vaccines, such as chimeric and Attenuated virus/bacteria vaccines, are produced in this manor.

In-VivoIn-Vivo

Embryonated Chicken eggs are commonly used as in producing flu vaccines.

Vaccines, like anti-idiotype, can also be produced in lab animals, such as mice.

There are even some species of plant, such as bananas, that have been genetically engineered to produce a vaccine.

Chemical SynthesisChemical Synthesis Produced in a lab.

Vaccines that utilize synthetic peptides as well as conjugated lipids and polysaccharides

Used in combination with either in-vivo or in-vitro production.

Summary!!!Summary!!!

Thank you!Thank you!