Vaccine Introduction Fahareen-Binta-Mosharraf MNS

The word “vaccine” originates from the Latin term Variolae vaccinae (cow pox) which Edward Jenner demonstrated in 1798 could prevent smallpox in humans. Today the term vaccine applies to all biological preparations, produced from living microorganisms, that enhance immunity against disease and either prevent (prophylactic vaccines) or, in some cases, treat (therapeutic vaccines) disease. Vaccines are administered in liquid form, either by injection, by oral, or by intranasal routes.

From living microorganisms that have been weakened, usually from cultivation under sub-optimal conditions (also called attenuation), or from genetic modification, which has the effect of reducing their ability to cause disease; From whole microorganisms that have been inactivated by chemical, thermal, or other means; From components of the disease-causing microorganism, such as specific proteins and polysaccharides, or nucleic acids; From inactivated toxins of toxin-producing bacteria; From the linkage (conjugation) of polysaccharides to proteins (this increases the effectiveness of polysaccharide vaccines in young children

What Does a Vaccine Contain? In addition to the bulk antigen that goes into a vaccine, vaccines are formulated (mixed) with other fluids (such as water or saline), additives or preservatives, and sometimes adjuvants.Collectively, these ingredients are known as the excipients. These ensure the quality and potency of the vaccine over its shelf-life. Vaccines are always formulated to be both safe and immunogenic when injected into humans. Vaccines are usually formulated as liquids, but may be freeze-dried (lyophilized) for reconstitution immediately prior to the time of injection.

 A vaccine is a biological preparation that improves immunity to a particular disease.  contains 1.an agent that resembles a disease-causing microorganism 2.made from weakened or killed forms of the microbe or its toxins  The agent stimulates the body's immune system to 1.recognize the agent as foreign 2.destroy it and 3."remember" it

Properties of ideal vaccine: Provide long lasting immunity. Should induce both humoral and cellular immunity. Should not induce autoimmunity or hypersensitivity. Should be inexpensive to produce, easy to store and administer. Vaccines must also be perceived to be safe.

Types of vaccine Live, attenuated vaccines Inactivated vaccines Subunit vaccines Toxoid vaccines Conjugate vaccines DNA vaccines Recombinant vector vaccines

KILLED VACCINES killed or inactivated normal (wild type) infectious, pathogenic microorganisms treatment with using heat, formaldehyde or gamma irradiation so that they cannot replicate at all convert to non pathogenic

 Advantages: Safe to use and can be given to immunodeficient and pregnant individuals. Cheaper than live attenuated vaccine Storage not as critical as live vaccine  Disadvantages: Since the microorganisms cannot multiply, a large number are required to stimulate immunity. Periodic boosters must be given to maintain immunity. Only humoral immunity can be induced. Most killed vaccines have to be injected

LIVE ATTENUATED VACCINE composed of live, attenuated microorganisms that cause a limited infection in their hosts sufficient to induce an immune response, but insufficient to cause disease

 Advantages: Infectious microbes can generate both memory and humoral immune responses. these can multiply in the host, fewer quantities must be injected to induce protection. Multiple booster doses may not be required. Whole microbes stimulate response to antigens in their natural conformation. They raise immune response to all protective antigens. Some live vaccines can be given orally; which gives more protection at the normal site of entry. Oral preparations are less expensive than giving injections

Disadvantages:  May very rarely revert to its virulent form and cause disease.  Live vaccines cannot be given safely to immuno suppressed individuals  Since they are live and because their activity depends on their viability, proper storage is critical.

SUBUNIT VACCINES contain purified antigens instead of whole organisms preparation consists of only those antigens that elicit protective immunity. composed of toxoids, subcellular fragments, or surface antigens effectiveness of subunit vaccines in increased by giving them in adjuvants. Adjuvants slow antigen release for a more sustained immune stimulation

Advantages: They can safely be given to immunosuppressed people They are less likely to induce side effects. Disadvantages: Antigens may not retain their native conformation, so that antibodies produced against the subunit may not recognize the same protein on the pathogen surface. Isolated protein does not stimulate the immune system as well as a whole organism vaccine

CONJUGATE VACCINES  primarily developed against capsulated bacteria  can act as subunit vaccine, they stimulate only humoral immunity- T independent immunity  generate short-lived immunity  covalently linking the polysaccharides to protein carriers, they are converted into T-dependent antigens and protective immunity is induced  Examples: Haemophilus influenzae HiB polysaccharide is complexed with diphtheria toxoid

RECOMBINANT VACCINES The vaccines are produced using recombinant DNA technology or genetic engineering Genes for desired antigens of a microbe are inserted into a vector Example: Hepatitis B Virus (HBV) vaccine is a recombinant subunit vaccine. Hepatitis B surface antigen is produced from a gene transfected into yeast (Saccharomyces cerevisiae) cells and purified for injection

Advantages: Those vectors that are not only safe but also easy to grow and store can be chosen. Antigens which do not elicit protective immunity or elicit damaging responses can be eliminated from the vaccine. Disadvantages: 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 immunodeficient individuals

Experimental vaccine  DNA vaccine  genes for the desired antigens are located and cloned.  The DNA is injected into the muscle of the animal being vaccinated, usually with a 1."gene gun“by bombarding the skin with DNA-coated gold particles 2.by nose drops

 Advantages: DNA is very stable, it resists extreme temperature and hence storage and transport are easy. A DNA sequence can be changed easily in the laboratory. The inserted DNA does not replicate and encodes only the proteins of interest.  Disadvantages: Potential integration of DNA into host genome leading to insertional mutagenesis. Induction of autoimmune responses: anti-DNA antibodies may be produced against introduced DNA.

Protein/polysacchaide-protein conjugate vaccine –immune response T-Dependent response:  Antibody production requires assistance from T helper cells.  A macrophage cells ingest antigen and peptide antigen presents it to T H cell.  T H cell stimulates B cells specific for antigen to become plasma cells.  Antigens are mainly proteins on viruses, bacteria, foreign molecules.

Polysaccharide vaccine –immune response T-Independent response:  Antibody production does not require assistance from T cells.  Antigens are mainly polysaccharides or lipopolysaccharides with repeating subunits (bacterial capsules).  Weaker immune response than for T-dependent antigens