History of vaccine

A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "recognize" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters. Vaccines can be prophylactic (e.g. to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen), or therapeutic (e.g. vaccines against cancer are also being investigated; see cancer vaccine). The term vaccine derives from Edward Jenner's 1796 use of the term cow pox (Latin variol vaccin, adapted from the Latin vaccn-us, from vacca cow), which, when administered to humans, provided them protection against smallpox.

Introduction
Human beings have benefited from vaccines for more than two centuries. Yet the pathway to effective vaccines has been neither neat nor direct. This paper explores the history of vaccines and immunization, beginning with Edward Jenners creation of the worlds first vaccine for smallpox in the 1790s. We then demonstrate that many of the issues salient in Jenners erasuch as the need for secure funding mechanisms, streamlined manufacturing and safety concerns, and deep-seated public fears of inoculating agentshave frequently reappeared and have often dominated vaccine policies. We suggest that historical awareness can help inform viable long-term solutions to contemporary problems with vaccine research, production, and supply. The gasping breath and distinctive sounds of whooping cough; the iron lungs and braces designed for children paralyzed by polio; and the devastating birth defects caused by rubella: To most Americans, these infectious scourges simultaneously inspire dread and represent obscure maladies of years past. Yet a little more than a century ago, the U.S. infant mortality rate was a staggering 20 percent, and the 1 childhood mortality rate before age five was another disconcerting 20 percent. Not surprisingly, in an epoch before the existence of preventive methods and effective therapies, infectious diseases such as measles, diphtheria, smallpox, and pertussis topped the list of childhood killers. Fortunately, many of these devastating diseases have been contained, especially in industrialized nations, because of the development and widespread distribution of safe, effective, and affordable vaccines. Indeed, if you asked a public health professional to draw up a top-ten list of the achievements of the past 2 century, he or she would be hard pressed not to rank immunization first. Millions of lives have been saved and microbes stopped in their tracks before they could have a chance to wreak havoc. In short, the 3 vaccine represents the single greatest promise of biomedicine: disease prevention. Nevertheless, the story is more complicated than it might appear at first glance. Even as existing vaccines continue to exert their immunological power and new vaccines offer similar hopes, reemerging and newly emerging infectious diseases threaten the dramatic progress made. Furthermore, obstacles have long stood in the way of the production of safe and effective vaccines. The historical record shows that the development of vaccines has consistently involved sizable doses of ingenuity, political skill, and

irreproachable scientific methods. When one or more of these has been lacking or perceived to be lacking, vaccination has engendered responses ranging from a revised experimental approach in the laboratory to a supply shortage and even insurrection in the streets. In short, vaccines are powerful medical interventions that induce powerful biological, social, and cultural reactions We begin our history of vaccines and immunization with the story of Edward Jenner, a country doctor 4 living in Berkeley (Gloucestershire), England, who in 1796 performed the worlds first vaccination. Taking pus from a cowpox lesion on a milkmaids hand, Jenner inoculated an eight-year-old boy, James Phipps. Six weeks later Jenner variolated two sites on Phippss arm with smallpox, yet the boy was unaffected by 5 this as well as subsequent exposures. Based on twelve such experiments and sixteen additional case histories he had collected since the 1770s, Jenner published at his own expense a volume that swiftly became a classic text in the annals of medicine: Inquiry into the Causes and Effects of the Variolae Vaccine. His assertion "that the cow-pox protects the human constitution from the infection of smallpox" 6 laid the foundation for modern vaccinology. How did Jenner, a country doctor, formulate the vaccine concept? To begin with, his discovery relied extensively on knowledge of the local customs of farming communities and the awareness that milkmaids infected with cowpox, visible as pustules on the hand or forearm, were immune to subsequent outbreaks of smallpox that periodically swept through the area. Moreover, a learned man immersed in the secular and rational doctrines of the Enlightenment, Jenner applied the scientific methods of observation and experimentation to this parochial wisdom, ultimately conducting one of the worlds first clinical trials. He thus was able to devise an alternative to variolation (the controlled transfer of pus from one persons active smallpox lesion to another persons arm, usually subcutaneously with a lancet), which had been 7 practiced in Asia since the 1600s and in Europe and colonial America since the early 1700s. Jenner also profited from his training as a wide-ranging generalist with a broad knowledge of science and medicine. For example, before devoting himself to private practice, Jenner focused on natural history, 8 penning well-respected studies of the cuckoo and the dormouse. In fact, Jenner was so skilled a naturalist that he was invited (although he declined) to join Captain Cooks second voyage to the South Seas to classify flora and fauna. Jenners interest in natural history and animal biology sharpened his medical understanding of the role of human-animal trans-species boundaries in disease transmission. He experienced the proverbial "Eureka"like moment sometime during the 1770s, after hearing a Bristol milkmaid boast, "I shall never have 9 smallpox for I have had cowpox. I shall never have an ugly pockmarked face." Two decades later he translated that farming lore into the guiding principle of his cowpox inoculation hypothesis. His cognizance that animals were implicated and necessary for vaccine production was truly prescient; it foreshadowed later use of cows, guinea pigs, rabbits, and even chicken eggs in vaccine production. However, this breach of the species barrier also made many people wary of and sometimes hostile to the idea of consciously introducing foreign animal products into their own bodies. During the early 1800s, for example, there was no shortage of cartoons mocking Jenner and depicting the transmogrification of the 10 recently vaccinated into sickly cows and fantastical beasts.

Type of vaccines.
Vaccines are dead or inactivated organisms or purified products derived from them. There are several types of vaccines currently in use.[5] These represent different strategies used to try to reduce risk of illness, while retaining the ability to induce a beneficial immune response.

Killed
Some vaccines contain killed, but previously virulent, micro-organisms that have been destroyed with chemicals or heat. Examples are the influenza vaccine, cholera vaccine, bubonic plague vaccine, polio vaccine, hepatitis A vaccine, and rabies vaccine.

Attenuated
Some vaccines contain live, attenuated microorganisms. Many of these are live viruses that have been cultivated under conditions that disable their virulent properties, or which use closelyrelated but less dangerous organisms to produce a broad immune response; however, some are bacterial in nature. They typically provoke more durable immunological responses and are the preferred type for healthy adults. Examples include the viral diseases yellow fever, measles, rubella, and mumps and the bacterial disease typhoid. The live Mycobacterium tuberculosis vaccine developed by Calmette and Gurin is not made of a contagious strain, but contains a virulently modified strain called "BCG" used to elicit immunogenicity to the vaccine.

Toxoid
Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than the micro-organism. Examples of toxoid-based vaccines include tetanus and diphtheria. Toxoid vaccines are known for their efficacy. Not all toxoids are for micro-organisms; for example, Crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites.

Subunit
Protein subunit rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine), a fragment of it can create an immune response. Examples include the subunit vaccine against Hepatitis B virus that is composed of only the surface proteins of the virus (previously extracted from the blood serum of chronically infected patients, but now produced by recombination of the viral genes into yeast), the virus-like particle (VLP) vaccine against human papillomavirus (HPV) that is composed of the viral major capsid protein, and the hemagglutinin and neuraminidase subunits of the influenza virus.

Conjugate
Conjugate certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to proteins (e.g. toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the Haemophilus influenzae type B vaccine.

Experimental
A number of innovative vaccines are also in development and in use:

Dendritic cell vaccines combine dendritic cells with antigens in order to present the antigens to the body's white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors.[6] Recombinant Vector by combining the physiology of one micro-organism and the DNA of the other, immunity can be created against diseases that have complex infection processes DNA vaccination in recent years a new type of vaccine called DNA vaccination, created from an infectious agent's DNA, has been developed. It works by insertion (and expression, triggering immune system recognition) of viral or bacterial DNA into human or animal cells. Some cells of the immune system that recognize the proteins expressed will mount an attack against these proteins and cells expressing them. Because these cells live for a very long time, if the pathogen that normally expresses these proteins is encountered at a later time, they will be attacked instantly by the immune system. One advantage of DNA vaccines is that they are very easy to produce and store. As of 2006, DNA vaccination is still experimental. T-cell receptor peptide vaccines are under development for several diseases using models of Valley Fever, stomatitis, and atopic dermatitis. These peptides have been shown to modulate cytokine production and improve cell mediated immunity. Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism[7].

While most vaccines are created using inactivated or attenuated compounds from microorganisms, synthetic vaccines are composed mainly or wholly of synthetic peptides, carbohydrates or antigens.

Valence
Vaccines may be monovalent (also called univalent) or multivalent (also called polyvalent). A monovalent vaccine is designed to immunize against a single antigen or single microorganism.[8] A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms.[9] In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune response.[10]

Developing immunity The immune system recognizes vaccine agents as foreign, destroys them, and "remembers" them. When the virulent version of an agent comes along the body recognizes the protein coat on the virus, and thus is prepared to respond, by (1) neutralizing the target agent before it can enter cells, and (2) by recognizing and destroying infected cells before that agent can multiply to vast numbers. When two or more vaccines are mixed together in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components. This phenomenon was first noted in the trivalent Sabin polio vaccine, where the amount of serotype 2 virus in the vaccine had to be reduced to stop it from interfering with the "take" of the serotype 1 and 2 viruses in the vaccine.[11] This phenomenon has also been found to be a problem with the dengue vaccines currently being researched, where the DEN-3 serotype was found to predominate and suppress the response to DEN-1, -2 and -4 serotypes.[12] Vaccines have contributed to the eradication of smallpox, one of the most contagious and deadly diseases known to man. Other diseases such as rubella, polio, measles, mumps, chickenpox, and typhoid are nowhere near as common as they were a hundred years ago. As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called herd immunity. Polio, which is transmitted only between humans, is targeted by an extensive eradication campaign that has seen endemic polio restricted to only parts of four countries (Afghanistan, India, Nigeria and Pakistan).[1] The difficulty of reaching all children as well as cultural misunderstandings, however, have caused the anticipated eradication date to be missed several times. The following questions should be asked when a vaccination policy against a particular virus is being developed. 1. 2. 3. 4. What proportion of the population should be immunized to achieve eradication. What is the best age to immunize? How is this affected by birth rates and other factors How does immunization affect the age distribution of susceptible individuals, particularly those in age-classes most at risk of serious disease? 5. How significant are genetic, social, or spatial heterogeneities in susceptibility to infection? 6. Hoe does this affect herd immunity?

Whole virus vaccines. either live or killed, constitute the vast majority of vaccines in use at present. However, recent advances in molecular biology had provided alternative methods for producing vaccines. Listed below are the possibilities;1. 2. 3. 4. 5. 6. Live whole virus vaccines Killed whole virus vaccines Subunit vaccines;- purified or recombinant viral antigen Recombinant virus vaccines Anti-idiotype antibodies DNA vaccines

1. Live Vaccines Live virus vaccines are prepared from attenuated strains that are almost or completely devoid of pathogenicity but are capable of inducing a protective immune response. They multiply in the human host and provide continuous antigenic stimulation over a period of time, Primary vaccine failures are uncommon and are usually the result of inadequate storage or administration. Another possibility is interference by related viruses as is suspected in the case of oral polio vaccine in developing countries. Several methods have been used to attenuate viruses for vaccine production. Use of a related virus from another animal - the earliest example was the use of cowpox to prevent smallpox. The origin of the vaccinia viruses used for production is uncertain. Administration of pathogenic or partially attenuated virus by an unnatural route - the virulence of the virus is often reduced when administered by an unnatural route. This principle is used in the immunization of military recruits against adult respiratory distress syndrome using enterically coated live adenovirus type 4, 7 and (21). Passage of the virus in an "unnatural host" or host cell - the major vaccines used in man and animals have all been derived this way. After repeated passages, the virus is administered to the natural host. The initial passages are made in healthy animals or in primary cell cultures. There are several examples of this approach: the 17D strain of yellow fever was developed by passage in mice and then in chick embryos. Polioviruses were passaged in monkey kidney cells and measles in chick embryo fibroblasts. Human diploid cells are now widely used such as the WI-38 and MRC-5. The molecular basis for host range mutation is now beginning to be understood. Development of temperature sensitive mutants - this method may be used in conjunction with the above method.

2. Inactivated whole virus vaccines These were the easiest preparations to use. The preparation was simply inactivated. The outer virion coat should be left intact but the replicative function should be destroyed. To be effective, non-replicating virus vaccines must contain much more antigen than live vaccines that are able to replicate in the host. Preparation of killed vaccines may take the route of heat or chemicals. The chemicals used include formaldehyde or beta- propiolactone. The traditional agent for inactivation of the virus is formalin. Excessive treatment can destroy immunogenicity whereas insufficient treatment can leave infectious virus capable of causing disease. Soon after the introduction of inactivated polio vaccine, there was an outbreak of paralytic poliomyelitis in the USA use to the distribution of inadequately inactivated polio vaccine. This incident led to a review of the formalin inactivation procedure and other inactivating agents are now available, such as Beta-propiolactone. Another problem was that SV40 was occasionally found as a contaminant and there were fears of the potential oncogenic nature of the virus. Live vs Dead vaccines Feature Dose low high no. of doses need for adjuvant Duration of immunity antibody response CMI Reversion to virulence Live single no many years IgG, good possible not Dead multiple yes less IgA IgG poor possible

Potential safety problems Live vaccines 1. 2. 3. 4. 5. 6. Underattenuation Mutation leading to reversion to virulence Preparation instability Contaminating viruses in cultured cells Heat lability Should not be given to immunocompromized or pregnant patients

Killed vaccines 1. Incomplete inactivation 2. Increased risk of allergic reactions due to large amounts of antigen involved

Present problems with vaccine development include 1. Failure to grow large amounts of organisms in laboratory 2. Crude antigen preparations often give poor protection. eg. Key antigen not identified, ignorance of the nature of the protective or the protective immune response. 3. Live vaccines of certain viruses can (1). induce reactivation, (2) be oncogenic in nature 3._Subunit Vaccines Originally, non-replicating vaccines were derived from crude preparations of virus from animal tissues. As the technology for growing viruses to high titres in cell cultures advanced, it became practicable to purify virus and viral antigens. It is now possible to identify the peptide sites encompassing the major antigenic sites of viral antigens, from which highly purified subunit vaccines can be produced. Increasing purification may lead to loss of immunogenicity, and this may necessitate coupling to an immunogenic carrier protein or adjuvant, such as an aluminum salt. Examples of purified subunit vaccines include the HA vaccines for influenza A and B, and HBsAg derived from the plasma of carriers. 4. Recombinant viral proteins Virus proteins have been expressed in bacteria, yeast, mammalian cells, and viruses. E. Coli cells were first to be used for this purpose but the expressed proteins were not glycosylated, which was a major drawback since many of the immunogenic proteins of viruses such as the envelope glycoproteins, were glycosylated. Nevertheless, in many instances, it was demonstrated that the non-glycosylated protein backbone was just as immunogenic. Recombinant hepatitis B vaccine is the only recombinant vaccine licensed at present. An alternative application of recombinant DNA technology is the production of hybrid virus vaccines. The best known example is vaccinia; the DNA sequence coding for the foreign gene is inserted into the plasmid vector along with a vaccinia virus promoter and vaccinia thymidine kinase sequences. The resultant recombination vector is then introduced into cells infected with vaccinia virus to generate a virus that expresses the foreign gene. The recombinant virus vaccine can then multiply in infected cells and produce the antigens of a wide range of viruses. The genes of several viruses can be inserted, so the potential exists for producing polyvalent live vaccines. HBsAg, rabies, HSV and other viruses have been expressed in vaccinia. Hybrid virus vaccines are stable and stimulate both cellular and humoral immunity. They are relatively cheap and simple to produce. Being live vaccines, smaller quantities are required for immunization. As yet, there are no accepted laboratory markers of attenuation or virulence of vaccinia virus for man. Alterations in the genome of vaccinia virus during the selection of recombinant may alter the virulence of the virus. The use of vaccinia also carries the risk of adverse reactions associated with the vaccine and the virus may spread to susceptible contacts. At present, efforts are being made to attenuate vaccinia virus further and the possibility of using other recombinant vectors is being explored, such as attenuated poliovirus and adenovirus.

5. Synthetic Peptides The development of synthetic peptides that might be useful as vaccines depends on the identification of immunogenic sites. Several methods have been used. The best known example is foot and mouth disease, where protection was achieved by immunizing animals with a linear sequence of 20 aminoacids. Synthetic peptide vaccines would have many advantages. Their antigens are precisely defined and free from unnecessary components which may be associated with side effects. They are stable and relatively cheap to manufacture. Furthermore, less quality assurance is required. Changes due to natural variation of the virus can be readily accommodated, which would be a great advantage for unstable viruses such as influenza. Synthetic peptides do not readily stimulate T cells. It was generally assumed that, because of their small size, peptides would behave like haptens and would therefore require coupling to a protein carrier which is recognized by T-cells. It is now known that synthetic peptides can be highly immunogenic in their free form provided they contain, in addition to the B cell epitope, Tcell epitopes recognized by T-helper cells. Such T-cell epitopes can be provided by carrier protein molecules, foreign antigens. or within the synthetic peptide molecule itself. Synthetic peptides are not applicable to all viruses. This approach did not work in the case of polioviruses because the important antigenic sites were made up of 2 or more different viral capsid proteins so that it was in a concise 3-D conformation. Advantages of defined viral antigens or peptides include: 1. 2. 3. 4. Production and quality control simpler No NA or other viral or external proteins, therefore less toxic. Safer in cases where viruses are oncogenic or establish a persistent infection Feasible even if virus cannot be cultivated

Disadvantages: 1. 2. 3. 4. May be less immunogenic than conventional inactivated whole-virus vaccines Requires adjuvant Requires primary course of injections followed by boosters Fails to elicit CMI.

6. Anti-idiotype antibodies The ability of anti-idiotype antibodies to mimic foreign antigens has led to their development as vaccines to induce immunity against viruses, bacteria and protozoa in experimental animals. Anti-idiotypes have many potential uses as viral vaccines, particularly when the antigen is difficult to grow or hazardous. They have been used to induce immunity against a wide range of viruses, including HBV, rabies, Newcastle disease virus and FeLV, reoviruses and polioviruses.

7. DNA vaccines Recently, encouraging results were reported for DNA vaccines whereby DNA coding for the foreign antigen is directly injected into the animal so that the foreign antigen is directly produced by the host cells. In theory these vaccines would be extremely safe and devoid of side effects since the foreign antigens would be directly produced by the host animal. In addition, DNA is relatively inexpensive and easier to produce than conventional vaccines and thus this technology may one day increase the availability of vaccines to developing countries. Moreover, the time for development is relatively short which may enable timely immunization against emerging infectious diseases. In addition, DNA vaccines can theoretically result in more long-term production of an antigenic protein when introduced into a relatively nondividing tissue, such as muscle. Indeed some observers have already dubbed the new technology the "third revolution" in vaccine developmenton par with Pasteur's ground-breaking work with whole organisms and the development of subunit vaccines. The first clinical trials using injections of DNA to stimulate an immune response against a foreign protein began for HIV in 1995. Four other clinical trials using DNA vaccines against influenza, herpes simplex virus, T-cell lymphoma, and an additional trial for HIV were started in 1996. The technique that is being tested in humans involves the direct injection of plasmids - loops of DNA that contain genes for proteins produced by the organism being targeted for immunity. Once injected into the host's muscle tissue, the DNA is taken up by host cells, which then start expressing the foreign protein. The protein serves as an antigen that stimulate an immune responses and protective immunological memory. Enthusiasm for DNA vaccination in humans is tempered by the fact that delivery of the DNA to cells is still not optimal, particularly in larger animals. Another concern is the possibility, which exists with all gene therapy, that the vaccine's DNA will be integrated into host chromosomes and will turn on oncogenes or turn off tumor suppressor genes. Another potential downside is that extended immunostimulation by the foreign antigen could in theory provoke chronic inflammation or autoantibody production

Presentation of immunogenic proteins and peptides Proteins separated from virus particles are generally much less immunogenic than the intact particles. This difference in activity is usually attributed to the change in configuration of a protein when it is released from the structural requirements of the virus particle. Many attempts have been made to enhance the immunogenic activity of separated proteins. Adjuvants Used to potentiate the immune response 1. Functions to localize and slowly release antigen at or near the site of administration. 2. Functions to activate APCs to achieve effective antigen processing or presentation Materials that have been used include;1. Aluminum salts 2. Mineral oils 3. Mycobacterial products, eg. Freud's adjuvants Immunostimulating complexes (ISCOMS) 1. 2. 3. 4. 5. 6. An alternative vaccine vehicle The antigen is presented in an accessible, multimeric, physically well defined complex Composed of adjuvant (Quil A) and antigen held in a cage like structure Adjuvant is held to the antigen by lipids Can stimulate CMI Mean diameter 35nm

In the most successful procedure, a mixture of the plant glycoside saponin, cholesterol and phosphatidylcholine provides a vehicle for presentation of several copies of the protein on a cage-like structure. Such a multimeric presentation mimics the natural situation of antigens on microorganisms. These immunostimulating complexes have activities equivalent to those of the virus particles from which the proteins are derived, thus holding out great promise for the presentation of genetically engineered proteins. Similar considerations apply to the presentation of peptides. It has been shown that by building the peptide into a framework of lysine residues so that 8 copies instead of 1 copy are present, the immune response induced was of a much greater magnitude. A novel approach involves the presentation of the peptide in a polymeric form combined with T cell epitopes. The sequence coding for the foot and mouth disease virus peptide was expressed as part of a fusion protein with the gene coding for the Hepatitis B core protein. The hybrid protein, which forms spherical particles 22nm in diameter, elicited levels of neutralizing antibodies against foot and mouth disease virus that were at least a hundred times greater than those produced by the monomeric peptide.

Vaccines : Malaysia
Jordan Bio-Industries Center (JOVAC)
Product Name BRUCE 19VAC BRUCEVAC ANTHRAVAC ORTHOVAC JOZAZEIT 1,2,4 Disease Brucella abortus Brucella melitensis Anthrax Camelpox Egg Drop Syndrome Type Live Live Live Live Killed B19 Rev 1 Sterne (34F2) JOUF 78 Not Available Strain Adjuvant Not Available Not Available Not Available Not Available Thiomersal and oil Thiomersal and oil Thiomersal and oil Not Available Not Available Not Available Not Available

JOVAZEIT 1,4

Egg Drop Syndrome

Killed

Not Available

JOVAZEIT 1,2,3,4

Egg Drop Syndrome

Killed

Not Available

AFTOVAC (monovalent) Foot and Mouth Disease Killed AFTOVAC (trivalent) AFTOVAC (Bivalent) GALLOVAC 9R Foot and Mouth Disease Killed Foot and Mouth Disease Killed Fowl Typhoid

O1 O1, A22, Asia1 O1, A22

Not 9R Available Live Nig 75/1

PESTEVAC

Peste des Petits Ruminants Sheep and Goat Pox Sheep and Goat Pox Sheep and Goat Pox

Not Available

JOVIVAC CAPRIVAC KENYAVAC

Live Live Live

RM-65 Gorgan SGP0240

Not Available Not Available Not Available

Malaysian Vaccines and Pharmaceuticals Product Name Name Not Available Disease Avian Influenza (Highly Pathogenic) Classical Swine Fever Type Strain Adjuvant Not Available

Not Not Available Available Live GPE Not Available Not Available

MVP Swine Fever GPE HSAP-VAC HSDA-VAC

Not Available Alum Not Available

Hemorrhagic Septicemia Killed Hemorrhagic Septicemia Killed

Veterinary Research Institute Product Name DVE-VAC HSDA-VAC HSAP-VAC S/GP-VAC Disease Duck Virus Enteritis Type Live Strain Malaysian 1345/93 B:2 B:2 Not Available Adjuvant None None Alum Alum

Hemorrhagic Septicemia Killed Hemorrhagic Septicemia Killed Sheep and Goat Pox Killed

A dosage form (DF) is the physical form of a dose of a chemical compound used as a drug or medication intended for administration or consumption. Common dosage forms include pill, tablet, or capsule, drink or syrup, aerosol or inhaler, liquid injection, pure powder or solid crystal (e.g., via oral ingestion or freebase smoking), and natural or herbal form such as plant or food of sorts, among many others. Notably, the route of administration (ROA) for drug delivery is dependent on the dosage form of the substance in question. Various dosage forms may exist for a single particular drug, since different medical conditions can warrant different routes of administration. For example, persistent nausea and emesis or vomiting may make it difficult to use an oral dosage form, and in such a case, it may be necessary to utilize an alternate route such as inhalational, buccal, sublingual, nasal, suppository, or parenteral instead. Additionally, a specific dosage form may be a requirement for certain kinds of drugs, as there may be issues with various factors like chemical stability or pharmacokinetics. As an example, insulin cannot be given orally because upon being administered in this manner, it is extensively metabolized in the gastrointestinal tract (GIT) before reaching the blood stream, and is thereby incapable of sufficiently reaching its therapeutic target destinations.

Types
Oral

Pill, tablet, or capsule Specialty tablet like buccal, sublingual, or orally-disintegrating Thin film (e.g., Listerine PocketPaks) Liquid solution or suspension (e.g., drink or syrup) Powder or liquid or solid crystals Natural or herbal plant, seed, or food of sorts (e.g., marijuana such as that found in "special brownies")

Inhalational

Aerosol Inhaler Nebulizer Smoking (often in natural herb (e.g., tobacco, marijuana) or freebase powder form (e.g., cocaine, methamphetamine) Vaporizer (usually to vaporize natural herbs like marijuana)

Parenteral Injection

Intradermal (ID) Intramuscular (IM) Intraosseous (IR) Intraperitoneal (IP) Intravenous (IV) Subcutaneous (SC)

Topical

Cream, gel, liniment or balm, lotion, or ointment, etc Ear drops (otic) Eye drops (ophthalmic) Skin patch (transdermal)

Suppository

Rectal (e.g., enema) Vaginal (e.g., douche, pessary, etc)

NAME : KAAMANISHA GOVINDASAMY

MATRIC NO. : PH106/10

LECTURER : MR. DHANA

TITLE : BLOOD