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Vaccination review

Published: June 10, 2020
By: Haroon Rashid Chaudhry / Lecturer IUB, Pakistan.
Definition:
Vaccination is an idea to enhance the protective immunity In an organism by inoculating an antigen or substance.
History:
The word vaccination is derived from a Latin word “vacca” meaning “cow”. Old females of Turkish nomads used to keep a needle (immersed in small pox lesion) with them. They used to use these needles to scratch the newborn. The newborn would develop a disease little bit but after some time newborn would recover and the newborn would had develop immunity against that disease.
Vaccination review - Image 1
In turkey British ambassador lord Montague’s son, who was living in England, was in those suffering from small pox disease as there was out break of small pox. He wrote a historical letter to Jenner to know about these happenings . Jenner observed the milkmaid hands and turkish action of needle . He took pus from cowpox lesion and developed the vaccine. Edward Jenner wanted to inject that vaccine in the son of Montague but he was strongly opposed by Queen and others. Jenner asked Montague for help and Montegue documented the permission letter. In which he said he himself will be responsible if any adverse effect of experiment will occur and sought permission from the queen for vaccination. After permission Jenner vaccinated the boy who after a mild ailment the boy recovered.  And thus he developed the vaccine against the smallpox disease. He termed this process as “variolation” (derived from “variola” smallpox) . Thus Edward Jenner is known as the father of vaccination.
Louis Pasteur worked on it and prepared many vaccines like Anthrax , Rabies and Fowl cholera and documented this work as vaccination. Pasteur named the current Vaccination from variolation. Pasteur later on established a company named “Pasteur Merieux” in France . it later on changed in “Rhone Poulenc” ( deals with human) and “Rhone Merieux” (dealing with animals). The company then converted into Sanofi Aventis.
Robert Koch and Pasteur belonged to rival countries. Koch worked on the disease and Pasteur worked on the prevention. This is the history of vaccination.
(Internet: Source)
Vaccines and vaccination
Immunoprophylaxis against viral illnesses include the use of vaccines or antibody- containing preparations to provide immune protection against a specific disease.
Active vaccines
Active immunization involves administrating a virus preparation that stimulates the body's immune system to produce its own specific immunity.
The principle of vaccination is to induce a "primed" state in the vaccinated subject so that following exposure to a pathogen, a secondary rapid immune response is generated leading to the accelerated elimination of the organism and protection from clinical disease.
Success depends on the generation of memory T and B cells and the presence in serum of neutralizing antibody.
Vaccines effectiveness is assessed in terms of percentage of recipients protected and the duration and degree of protection. Most effective viral vaccines protect more than 90% of recipients and produce fairly durable immunity.
Attributes of a good vaccine:
  1. Ability to elicit the appropriate immune response for the particular pathogen.
  2. Long-term protection (ideally life-long).
  3. Safety - the vaccine itself should not cause a disease.
  4. Stable - retain immunogenicity, despite adverse storage conditions prior to administration.
  5. Inexpensive.
Live vaccines:
  1. Live attenuated organisms - organisms whose virulence has been artificially reduced by in vitro culture under adverse conditions such as reduced temperature. This results in the selection of mutants which replicate poorly in the human host, and are therefore of reduced virulence. Replication of the vaccine strain in the host reproduces many of the features of wild type infection, without causing a clinical disease. The immune response is usually good - when the virus replicates in the host cells, both humoral and cell-mediated immune responses are generated and immunity is generally long-lived. Often, only a single dose is needed to induce long-term immunity.
  2. Heterologous vaccines - closely related organism of lesser virulence, which shares many antigens with the virulent organism. The vaccine strain replicates in the host and induces an immune response that cross reacts with antigens of the virulent organism
  3. Live recombinant vaccines – it is possible, using genetic engineering, to introduce a gene coding for an immunogenic protein from one organism into the genome of another. The organism expressing the foreign gene is called recombinant. 
Following injection into the subject, the recombinant organism will replicate and express sufficient amounts of the foreign protein to induce a specific immune response to the protein.
Advantages of live vaccines:
  • Induce global immune response (cellular, humoral and local).
  • Immune response against all antigens (inactivation may alter antigenicity).
  • Immunity after natural administration (cheap to prepare, good acceptability).
  • Good immunity after first dose.
  • Possibility of dissemination from the vaccinees to contacts, eliminating the virus from collectivity.
Disadvantages of live vaccines:
  • Not stable to transport.
  • Interference with similar viruses.
  • Severe reaction in immunossupresst.
  • May induce disease in some cases.
  • Contamination with oncogen agents.
Killed (inactivated) vaccines:
The organism is propagated in bulk, in vitro, and inactivated with either
β-propiolactone or formaldehyde.
These vaccines are not infectious and are therefore relatively safe, however they are usually of lower immunogenicity and multiple doses may be needed to induce immunity. In addition, they are usually expensive to prepare.
  • Subcellular fractions - when protective immunity is known to be directed against only one or two proteins of an organism, it may be possible to use a purified preparation of these proteins as a vaccine. The organism is grown in balk and is inactivated, and then the protein of interest is purified and concentrated from the culture suspension.
These vaccines are safe and fewer local reactions occur at the injection site, however it has the same disadvantages of poor immunogenicity and the need for multiple boosters applies.
  • Recombinant proteins - immunogenic proteins of virulent organisms may be synthesized artificially by introducing the gene coding for the protein into an expression vector.
The protein of interest may be extracted from lysates of the expression vector, then concentrated and purified for use as a vaccine. Example for this type of vaccine is the hepatitis B vaccine.
Advantages of killed vaccines:
  • Since it is inactive it cannot replicate in the host and cause disease.
  • Efficacy of the vaccine does not rely on the viability of the organisms, so these vaccines tend to be able to withstand more adverse storage conditions.
Disadvantages of killed vaccines:
  • Poor immune response (no cell-mediated immune response).
  • The response is short-lived and multiple doses are needed.
  • Local reactions at the site of injection may occur.
  • Expensive to prepare.
Immunogenicity may be enhanced by the incorporations of adjuvants into the vaccine preparation.
There are several possible modes of action for adjuvants:
  • By trapping antigen in the tissues, thus allowing maximal exposure to dendritic cells and specific T and B lymphocytes.
  • By activating APCs to secrete cytokines that enhance the recruitment of antigen-specific T and B cells to the site of inoculation.
DNA vaccines:
Are experimental at present, but have a promise future since they evoke both humoral and cell-mediated immunity, without the dangers associated with live virus vaccines.
The gene for an antigenic determinant of a pathogenic organism is inserted into a plasmid. This genetically engineered plasmid comprises the DNA vaccine which is then injected into the host.
Within the host cells, the foreign gene can be expressed (transcribed and translated) from the plasmid DNA, and if sufficient amounts of the foreign protein are produced, they will elicit an immune respone.
Passive vaccines
Passive immunization is the transfer of immunity to a host by means of immunoglobulins (preformed antibodies).
Immunoglobulins from immune individuals can be used as prophylaxis to prevent viral infections in exposed, but non-immune individuals.
It works by binding to extracellular virions and preventing them from attaching to and entering susceptible cells. The protective effect is short-lived (up to 3 months) because the antibodies are metabolized in the host.
  • "Normal" immune globulin - this is a pooled product, prepared from the serum of normal blood donors. It contains low titres of antibody to a wide range of human viruses. It is mainly used as prophylaxis against hepatitis A vitus infection.
  • Hyper-immune globulin - immunoglobulin may be prepared from the serum of selected individuals who have high titres of antibody to particular viruses.
For example Zoster immunoglobulin (prevention of Varicella in immunocompromised children and neonates) and Human Rabies immunoglobulin (post-exposure prophylaxis).
Passive immunity is also available in maternal milk, as it contains some antibodies from the mother which are transformed to the newborn. (Source: Internet notes)
Types of vaccination
Vaccines can be divided as
  • Homo-vaccines
  • Hetero-vaccines
Homo-vaccines:
Vaccine that are prepared from one species and are used in that species. For example vaccine of cat is being vaccinated in cats.
Hetero-vaccines:
The vaccines that are used intraspecies are known as hetero-vaccines. For example cowpox vaccine is being used in human.
Vaccines can also be divided as
  • Live vaccines
  • Killed vaccines
Live vaccines:
            In case of live vaccines we introduce live antigen into the body. Live vaccines are mostly used in case of viruses(90%). Sometimes these are also used in case bacteria but very less e.g. in case of  anthrax and TB. Live vaccines have following benefits:
  • Easy to handle.
  • Easy to administer.
  • Beneficial in herd management. It can be sprayed and can also be delivered through water. Live vaccines is subdivided as :
    • Wild type
    • Attenuated type
Wild type:
This include virus and bacteria
Anthrax: it may be
  • PA based
  • Lethal Factor based
  • Cap B wild base
New castle disease virus (NDV): it may include:
  • Cold strain
  • Mild strain
  • Intermediate strain                                                                                                              
Infectious bursal disease (IBD)
  • Cold strain
  • Mild strain
Intermediate strain
Hot strain
Attenuated/weakened type:
An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live"). Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. Attenuation is done by changing the media
Examples:
BCG against TB virus:
Attenuation is done by keeping in highly enrich media due to which it gradually loses it pathogenicity.
Rabies vaccine:
Rabies virus normally grows in mammals but for the attenuation we grow it in the egg. It looses its pathogenicity as media is changed.
NOTE:
Live vaccines are not preferred when:
  • Virus or bacteria can mutate and the case may be adverse as seen in case of bird flu virus and influenza virus.
  • Reversion can take place.
  • When case fatality is very high.
Killed vaccines:
An inactivated vaccine (or killed vaccine) is a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then killed using a method such as heat or formaldehyde.          
Following methods are used to inactivate the viruses:
  • Heat
  • Chemicals
  • UV lights
Heat:
Heat causes uncontrolled denaturation which is not needed so heat is no more used for inactivation.
UV light:
UV light causes the mutation so that it is also not used.
Chemicals:
In chemical inactivation following chemicals are used:
Formaldehyde but it is not used in human.
Alum is also used.
In chemical inactivation controlled addition of the inactivants (chemicals) is done.
Routes of vaccination  
The route of administration is the path by which a vaccine (or drug) is brought into contact with the body.
The choice of route is of vital importance because incorrect route causes vaccine failure resulting in no immune response.
Live vaccines may be administered through the following routes:
Oral
Intra-nassal
Intra-occular/conjunctival
Note:
Live vaccines are mostly used in flock management. In flock management spray is preferred which cover the above mentioned route. In this way no animal is skipped from vaccination. In this method signs, symptoms, and morality are not observed but the replication is going on in the body and morbidity also occur.
Rules for vaccination:
  • To initiate the immune response.
  • Live vaccines are used mostly used orally, intra-nassal & intra-ocuular.
  • Vaccines should not cause disease but replicate and spread.
  • Vaccines must be temperature and chemical tolerant.
Oral:
Vaccine that is orally used should be temperature tolerant. That is why vaccines are often kept in cooler or iceboxes such as vaccines against polio. Vaccines that are orally used are
  • Sabien stain→ used for polio.
  • Rota virus vaccine→ Rota virus is one pf the biggest cause of diarrhea.
  • cholera
Intranasal:
Not much popular in human but frequently used in veterinary. For example it is used in herd, flock management. It is done with the help of spray.
Note:  In flock or herd management intraocular, intranasal and oral are used in combined way as these three parts are interconnected.
In case of poultry following vaccines are given by routes mentioned above:
  • ND vaccines
  • Infectious bursal disease
  • Infectious bronchitis
These are given through
Water supply→ mixed in water tank and then delivered to the flock. For this purpose chicks are kept away from water to make them  thirsty  so that they could desire for water. Then the water in which vaccine is mixed is delivered to the flock.
spray→ in case of spray the size of droplet is under consideration.
Intradermal vaccine:
In this route of vaccine a very minute amount of vaccine is required so  this route of vaccine is economic for vaccinator.
Vaccine of rabies and TB is done through this route. Vaccine is live enough to replicate and spread.
Subcutaneous:
When vaccine contain oil (mineral oil & montanite oil) and formalin then this route is not used. Mostly killed vaccines are given through this route. For this route alum precipitate or aluminum gel is used. Following vaccines are done through this route:
  • FMD vaccine
  • Clostridial vaccine
  • HS vaccine 
Intramuscular:
  • The vaccines containing oil and formalin are given through this route.
  • For human and cats, dogs & equines mostly β-propiolactone and gel is used.
  • For animals(cattle & buffalo) oil and formalin is used.
Followings are the benefits of the
  • Its reaction time is fast.
  • Continuous release so long lasting effect.
  • Long lasting titter.
FMD & HS vaccines for long lasting effects can be given through this route.
Intravenous:
In this route of vaccine is very low success rate. Modern vaccines like DNA, RNA, and recombinant vaccines are given through this route. It is vector based. Genome must be active and vector must be alive. Conventional vaccines are not done through this route.
Bone merrow:
It is also a modern and expensive method of vaccine. The success rate is very low also in this method.
Fruit vaccines:
For this method recombinant fruits and vegetables can be used. Super candy is another good example in this regard which is being tested for vaccination.
Vaccine patch:
This is experimental method up-till now. Nano technology is being used in this method. The vaccine patch contain the Nano needles which contain vaccine. (micro injections)
Water bubble/ drop:
Drop of water containing vaccine is enclosed inside a capsule which is made up of sea weed carbohydrate. This drop is being tested for vaccination.
Intra-cerebral:
           
WHAT IS INSIDE THE DOSE OF A VACCINE:
1.ACTIVE INGREDIENT:
  • Component which performs the actual function is the active ingredient. Active ingredient in vaccine is immunogen/antigen. This immunogen can be dead/killed (killed vaccine), live (live vaccine), protenacious (subunit vaccine)
BIOLOGICAL TITRE
  • The number of organisms that die & remain alive after experimental infection of an organism
  • Dose at which mortality is reduced by 50%
  • Also called as protective dose
IN-VITRO TITRE:
  • Number of antibodies raised by a vaccine
2. VEHICLE/DILUENT:
  • To be put into vaccine
  • Vehicle in case of human vaccine is sterile water
  • For more effectiveness, oil is used as vehicle (usually not used), otherwise distilled water, or combination of both
3. BUFFER:
  • Buffer is added with vehicle
  • Usually vehicle & buffers are used as a single buffered solution
  • Phosphate buffer saline (PBS) is used
4.ADJUVANT:
  • It increases or decreases the efficiency of a drug or vaccine indirectly
  • It increases the retention of vaccine in a tissue
  • It provides aid to a vaccine
Following are some common adjuvants:
ALUMINIUM HYDROXIDE:
  • Increases efficiency
  • Increases the retention of immunogen in the tissue
  • Classical adjuvant for humans, horses, poultry & dogs
  • Less toxic
  • Immunity provided is short lived (maximum 3-6 months depending upon immunogen)
  • Cannot be used in live vaccine
OIL:
  • Extremely toxic
  • Cannot be given through sub-cutaneous route
  • Always given through IM route
  • Long duration
  • Used in cattle/buffaloe
  • For example, mineral oil, montanide oil (long acting, can generate immunity upto one year)
  • Oil & water form emulsion (oil works as emulsifier), which improves the retention time of immunogen
SAPONINS:
  • They are costly
  • Used for humans
  • \Not used on veterinary side
v No adjuvant is used in live vaccine
5. INACTIVANT:
  • Should be present to inactivate bacteria or virus
  • Used only in killed vaccine
  • Involves acids, disinfectants, chemicals, ultrasonic waves, heat, phenol, iodine salts
  • Formalin is used as inactivant commercially (0.25-0.5ml added for 24/48 hours)
  • Glycerol (glycerine), phenol is also used as inactivant
  • Formalin is not used as inactivant in humans, horses, dogs & cats
  • Formalin is used in cattle/buffaloe
  • Binary ethanalimine (BEI) is used as inactivant in viral diseases (degrades viral RNA). It is toxic & bound to sodium thiosulphate for neutralizing BEI
  • Change in antigen should be minor otherwise antibody will not bind to antigen. Change in antigen should be mild
  • Inactivants are never added to live vaccines otherwise it will no longer remain live.
6. EXCIPIENTS:
  • Excipients are not the part of drug. They are the part of solution.
  • They do not have a direct influence.
  • Include buffers (PBS)
  • Include taste changers (e.g sucrose, glucose, glycine)
  • Include stabilizers
  • Skimmed milk is used as stabilizer in veterinary (poultry)
  • Albumin is used as stabilizer in humans
7.PRESERVATIVES:
  • They prevent the growth of bacteria, virus, fungi in vaccines
  • For example, phenol is used as a preservative
  • In vaccines of humans, Thiomersal sodium is used
  • For diagnostic purpose, sodium azide is used
  • 2-phenoxyethanol is also used as a preservative in human vaccines but it is costly
8.SURFACTANTS:
  • They reduce the surface tension
  • Tween 80 detergent is used
  • Omegas are used in  polio/live vaccines
9.RESIDUALS:
  • The growth media in which vaccine is made is called residual
  • Residuals can be live animals, eggs, cell cultures, broth
  • Mostly vaccines are made in broth
  • Residuals should be in minimum quantity & should be diluted because they can cause allergy
  • Degrading enzymes e.g DNAses, RNAses, carboxyhydrases, lipases, peptidases  also move into the vaccine alongwith residuals. Stabilizers do not let degrading enzymes work. Buffers maintain the pH after addition of degrading enzymes
HOW LIVE VACCINES WORK:
Live vaccines are not injected. For example, polio vaccine in humans, ND vaccine in poultry
WORKING:
NEW CASTLE DISEASE (ND):
When live vaccines are given e.g ND vaccine in poultry, the virus will replicate in the sinuses. As a result, number of viruses will increase. The virus will get processed in crop, gizzard & then gets out of the body. The virus will replicate throughout the body of the bird. It will be attacked by MHC-1 & will activate T & B cells.
  • Replication is necessary for live virus vaccines to work
POLIO:
Polio virus is a GIT virus. It will replicate but does not cause disease.
  • If the polio virus does not replicate, the child will not get vaccinated because live virus vaccines require virus to replicate for their working.
COLD STORAGE OF VACCINES:
  • Increase in temperature enhances the ability of the degrading enzymes (DNAses, RNAses) that digest DNA, RNA, immunogens etc, therefore cold storage of vaccines is necessary.
  • To protect from sunlight, vaccines are kept in brown bottles or bottles made up of dark plastic.
  • Vaccine bottles are packed in large & good cartons (brown colored) that prevent the sunlight from entering otherwise denaturation occurs, and this occurs due to activity of degrading enzymes acquired from residuals..
  • Cold storage must be maintained. Temperature must not exceed 4°, otherwise denaturation occurs, and this occurs due to activity of degrading enzymes acquired from residuals.
  • Cold storage includes large refrigerated rooms. Vaccination thermos is used in which ice packs are placed
COLD CHAIN:
  • Cold chain means to maintain the cold storage of vaccines from the production unit to the consumer. Throughout this, temperature must not exceed 4°.
  • Polio virus is thermoresistant (not heat sensitive)
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