Vaccines - eacademic.ju.edu.jo

Vaccines

1 Ch1.Infections and Vaccines

http://www.theimmunology.com/animati

ons/Vaccine.htm

http://www.theimmunology.com/animations/Vaccine.htm


Ch1.Infections and Vaccines 2

ORGANISMS That can

EVADE THE IMMUNE

RESPONSE

HOW ORGANISMS EVADE THE IMMUNE RESPONSE Viruses

Small RNA viruses, such as influenza and HIV small genomes so can not encode proteins to evade the immune response.

•BUT their RNA genome tends to mutate, RNA virus antigenic proteins change continually evade immunologic memory.

• HIV this can happen within an individual. over just a few months of infection.

•Influenza mutates more slowly across a population rather than in an individual.

DNA viruses are larger and have capacity in their genomes for evasion tools.

•Some DNA viruses (members of the herpes virus family)evade the adaptive immune response by downregulating (MHC) expression, and the innate response is required for their control (natural killer [NK] cells).

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Ch1.Infections and Vaccines

Bacterial pathogens different strategies to evade:

Extracellular : Pneumococcus (Streptococcus pneumoniae) and Haemophilus sp. evade the innate response (opsonization by complement and phagocytosis) by producing a polysaccharide capsule successful pathogens of the respiratory tract.

Intracellular: • Mycobacteria, such as M. tuberculosis, have waxy coats that block the effects of phagocyte enzymes. They also secrete catalase, which

inhibits the effects of the respiratory burst.

• Listeria

cause meningitis, particularly in pregnant women.

Listeria secrete listeriolysin, which punches holes in the phagolysosome walls.

The bacteria can then escape into the cytoplasm, where they are not exposed to the toxic products of the metabolic burst or to proteolytic enzymes.


• Phagocytic mechanisms:

– Ingestion: formation of phagolysosomes

• Respiratory Bursts: merge phagosome with lysosome & flood phagolysosome with free radicals (macrophage)

• Defensins: proteins that crystallize out of solution & pierce pathogen membranes (neutrophils)

5 Introduction to the Immune system and

Innate Immunity

Mechanism of Immunity • Most primary infections ( except TB, HIV, herpes viruses)are completely

cleared by the immune system sterilizing immunity.

• Immunologic memory develops subsequent exposure to the same pathogen elicits a memory response by the adaptive immune system so infection is prevented or symptoms reduced.

• After maternal antibody lost early childhood a series of primary infections while effective immunologic memory is developed.

• Vaccination can act as a substitute for primary infection allowing immunologic memory to develop without a symptomatic primary infection.

• Vaccines are a success story; smallpox completely eradicated .

• Many other infections (polio, diphtheria & pertussis) become relatively rare.

• Passive immunotherapy the transfer of adaptive immunity-usually antibodies-from one individual to another give protective antibodies to an individual exposed to a pathogen.

• Some cases might need both

- passive immunotherapy (to reduce the immediate risk of infection) and - the vaccine (to induce immunologic memory and reduce the risk for future infection). 6 Ch1.Infections and Vaccines


• Antigen in form of infection or Vaccine develops Active Immunity Immunologic immunity develops and protects individual from reinfection.

• There are various types and compositions of vaccine

• Most vaccines elicit antibodies, and some elicit T-cell responses. Antibodies Can be neutralizing antibodies prevent pathogens from binding onto

target cells or prevent the actions of toxins released from pathogens Another Antibodies activate complement, and stimulate phagocytosis and NK cell-mediated killing.

CD8+ T cells inhibit viral replication by secreting interferons or, more often, kill infected cells.

Types of Vaccines:

Live Vaccines

Killed Organisms

Subunit Vaccines


Types of Vaccine


• Live Vaccines (Viruses or Bacteria) First discovered and the most effective ones.

very successful smallpox and polio are live vaccines.

use non virulent organisms (organisms that have evolved to grow in animals); although they replicate in healthy vaccine recipients, they do not cause disease.

Live vaccines are very effective for three reasons

1. They replicate and thus deliver sustained doses of antigen. 2. They replicate intracellularly so they deliver antigenic peptides to (MHC)

class I stimulate cytotoxic T cells (CTLs).

3. They replicate at the anatomical site of infection, further focusing the immune response live vaccines given by nose or by mouth elicit IgA Abs.

Attenuated live vaccines cause serious infections in immunodeficiency patients Occasionally, live vaccines viruses may spontaneously revert to the virulent wild-type organism.

Attenuated polio vaccine differs from wild-type virus in 10bp make it easy for the virus to mutate back to the virulent form. This has been identified in water supplies. So USA has started to use killed polio vaccine once more. 10



Killed Organisms (Viruses or Bacteria)

Generally not as effective as live vaccines at eliciting a protective immune response.

Theoretically much safer Killed vaccines - do not replicate in hosts and - cannot enter intracellular antigen presenting pathways.

Subunit Vaccines (Toxoids, recombinant, polysaccharides and DNA)

Subunits are components of pathogens induce predominantly antibody responses.

Can be prepared by destroying virulent organisms, purifying the subunit, and then inactivating it so that it cannot cause disease.

Other subunits are prepared using recombinant technology.




Toxoids: Subunits purified from organisms and then inactivated

usually bacterial exotoxins chemically altered to make them safe.

The neutralizing antibodies produced block the effects of the toxins.

Diphtheria and tetanus toxoid are good examples

Subunit and toxoid vaccines of low immunogenicity compared with intact

organisms, and they may need adjuvants to work effectively.

Recombinant Virus Hepatitis B vaccine is a subunit antigen that has been produced

using recombinant techniques (made up of recombinant virus surface peptide)

Antibodies raised against surface peptide will prevent the virus attaching to and then entering liver cells.

Up to now, hepatitis B vaccine has been very effective.


Recombinant Virus vaccine


1 2 3

4

Hepatitis B vaccine

Capsular polysaccharides

Polysaccharides are very poor immunogens, largely because they rely on the response of T-independent B cells and do not make good vaccines.

To overcome this, effective vaccines contain polysaccharide that has been chemically conjugated to a peptide antigen: tetanus toxoid is often used.

T cells responding to the peptide then provide help for B cells responding to the polysaccharide

DNA vaccine: In this experimental approach, the gene for the immunogenic protein is coated onto gold microspheres and injected directly into cells (e.g., of the skin).

In mice, this has resulted in antibody production, indicating that the genes were transcribed


Adjuvants • Weaker antigens or subunits vaccines may be rendered more immunogenic by

the addition of other chemicals. Such chemicals are known as adjuvants.

• They provide the danger signal required for the innate immune system to release signals to drive antibody and T-cell responses.

• Live vaccines generally do not require adjuvants because they are capable of providing danger signals and stimulating Toll-like receptors (TLRs) themselves.

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http://www.vetscite.org/publish/articles/000027/print.html

For example, bacille Calmette-Guérin (BCG), the live vaccine for tuberculosis, produces large quantities of bacterial sugars, which activate TLRs 2 and 4. Killed whole vaccines also contain substances that activate TLRs and can act as adjuvants.





• Aluminum hydroxide (alum) is the only adjuvant licensed and used routinely in human vaccines.

• It is used to boost the effects of a wide variety of subunit vaccines.

• Aluminum hydroxide

activates macrophages, which then secrete inflammatory cytokines

and present antigen to T and B cells.

• Aluminum is not a powerful adjuvant

• Polynucleotide: Two new approaches are being used to create improved adjuvants.

One in vaccine molecules, which activate TLRs. These include molecules such as unmethylated cytosine and guanine sequence (CpG) motifs that have been shown to improve the antigenicity of several subunit vaccines.


• Subunit vaccines do not enter the intracellular antigen processing pathways so do not elicit cytotoxic T cell (CTL) responses.

• CTL responses are particularly important in dealing with intracellular infections such as HIV.

• Immunostimulatory complexes (ISCOMs) promotes CTL responses.

• ISCOMs are micelles of lipid and subunit antigen that are lipophilic and able to penetrate cell membranes.

• ISCOMS have two special advantages over conventional vaccines:

The antigen penetrates the cell membrane

and is delivered to the antigen-presenting pathways.

• SO stimulate T cells, including CTL.

• ISCOMs can be used for mucosal vaccines (e.g., through the nose) and induce widespread mucosal immunity in the gut and respiratory tract

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VACCINE SCHEDULES • Vaccine schedules take into account the clinical implications

of each type of infection.

• For example, the main purpose of rubella vaccine – is to prevent intrauterine infection (which can cause

birth deformities), so there is little point in giving it before puberty.

• On the other hand, it would be desirable to protect very young infants against Haemophilus,

– because this organism causes most damage at this age

• However, even as conjugate vaccines, polysaccharides do not elicit antibodies in newborn babies



•Vaccine schedules also vary in different parts of the world

in the developing world, measles is a major cause of death in

infants and so the vaccine is given as early as possible.

In the developed world, measles has become rare and tends to

affect school age children, so the vaccine can be given slightly

later.

•The main factor affecting the use of vaccines in the developing world

is, however, cost.






Cancer Vaccines


http://pathology2.jhu.edu/pancreas/vac_anim.htm




Cancer Vaccines • To harness the body's defense system in the fight

against cancer

• What is a cancer vaccine?

• A composition which can stimulate the immune system – Normally against infectious diseases (ex. viruses)

– Antibodies

– Killer T-cells ***

• Killer T-cells are more effective against cancerous cells


Therapeutic vs. Preventative

• Most vaccines are preventative:

– Given before the individual becomes infected/acquires diseases

• Cancer vaccines are therapeutic

– Administered to individuals after they already have cancer

– Goal- eliminate existing cancer cells

– One day we may be able to give preventative vaccines….


Types of vaccines • A cancer vaccine can be made:

– either of whole tumor cells – substances contained by the tumor, called antigens

• whole cell vaccine – tumor cells are taken out of the patient(s), and grown in the

laboratory – tumor cells are treated

• They can no longer multiply • There is nothing present that could infect the patient

• when whole tumor cells are injected into a person, an immune response against the antigens on the tumor cells is generated


Types of whole cell cancer vaccines • An autologous whole cell vaccine is made with your

own whole, inactivated tumor cells

• An allogenic whole cell vaccine is made with someone else’s whole, inactivated tumor cells or several peoples' tumor cells combined



http://www.biocreations.com/animations/TumorVac_demo.swf

http://www.biocreations.com/animations/TumorVac_demo.swf

Antigen vaccines

• Made of whole cells, but of one or more substances (called antigens) contained by the tumor

– One tumor can have many antigens

– Some antigens are common to all cancers of a particular type,

– and some antigens are unique to an individual (a few antigens are shared between tumors of different types of cancer)


Antigen delivery mechanisms

1. Proteins or pieces of protein from the tumor cells can be given directly as the vaccine.

2. Genetic material coding for those proteins can be given (RNA or DNA vaccine).

3. A virus can be enlisted to help deliver the antigen. Viruses used in this way are called viral vectors, and do not make people sick or carry any diseases. The virus is capable of infecting only a small number of human cells-- enough to start an immune response, but not enough to make a person sick.

4. Viruses can also be engineered to make cytokines or display proteins on their surface that help activate immune cells. These can be given alone or with a vaccine to help the immune response. 33 Ch1.Infections and Vaccines


Prospects for cancer vaccines

• Laboratory animals:

– When cancer vaccines are studied in laboratory animals, cancer vaccines that stimulate the immune system can cause tumors to withdraw

• In humans:

– Tumors have learned to escape the immune system, and the immune system is not fighting tumors effectively


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Vaccines - eacademic.ju.edu.jo