Facts About Vaccine

We are hearing these days that there is only solution to the Corona pandemic is vaccination.Here we are trying to through some light on what is vaccine,history,its stage of development,and types.

A vaccine is a biological preparation that provides active acquired immunity to a particular infectious disease.^[1] A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future. Vaccines can be prophylactic (to prevent or ameliorate the effects of a future infection by a natural or "wild" pathogen), or therapeutic (to fight a disease that has already occurred, such as cancer).Edward Jenner hs developed the first vaccine Variolae vaccine (smallpox of the cow) known as the cowpox.His method underwent medical and technological changes over the next 200 years, and eventually resulted in the eradication of smallpox.

Louis Pasteur’s 1885 rabies vaccine was the next to make an impact on human disease. And then, at the dawn of bacteriology, developments rapidly followed. Antitoxins and vaccines against diphtheria, tetanus, anthrax, cholera, plague, typhoid, tuberculosis, and more were developed through the 1930s.

The middle of the 20th century was an active time for vaccine research and development. Methods for growing viruses in the laboratory led to rapid discoveries and innovations, including the creation of vaccines for polio. Researchers targeted other common childhood diseases such as measles, mumps, and rubella, and vaccines for these diseases reduced the disease burden greatly.

Innovative techniques now drive vaccine research, with recombinant DNA technology and new delivery techniques leading scientists in new directions. Disease targets have expanded, and some vaccine research is beginning to focus on non-infectious conditions such as addiction and allergies.

Different Types of Vaccines

Vaccines are made using several different processes. They may contain live viruses that have been attenuated (weakened or altered so as not to cause illness); inactivated or killed organisms or viruses; inactivated toxins (for bacterial diseases where toxins generated by the bacteria, and not the bacteria themselves, cause illness); or merely segments of the pathogen (this includes both subunit and conjugate vaccines).

Inactivated

Some vaccines contain inactivated, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, or radiation.Examples include the IPV polio vaccine, hepatitis A vaccine, rabies vaccine and most influenza vaccines.

Attenuated

Some vaccines contain live, attenuated microorganisms. Many of these are active viruses that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases yellow fever, measles, mumps, and rubella, and the bacterial disease typhoid. The live Mycobacterium tuberculosis vaccine developed by Calmette and Guérin is not made of a contagious strain but contains a virulently modified strain called "BCG" used to elicit an immune response to the vaccine. The live attenuated vaccine containing strain Yersinia pestis EV is used for plague immunization. Attenuated vaccines have some advantages and disadvantages. Attenuated, or live, weakened, vaccines typically provoke more durable immunological responses. But they may not be safe for use in immunocompromised individuals, and on rare occasions mutate to a virulent form and cause disease.

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

Rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine), a subunit vaccine uses a fragment of it to 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) or as an edible algae vaccine, 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. A subunit vaccine is being used for plague immunization.

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.

Heterotypic

Also known as heterologous or "Jennerian" vaccines, these are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of BCG vaccine made from Mycobacterium bovis to protect against human tuberculosis.

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 and are also tested in malignant melanoma.

· DNA vaccination – The proposed mechanism is the insertion and expression of viral or bacterial DNA in human or animal cells (enhanced by the use of electroporation), triggering immune system recognition. 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 potential advantage of DNA vaccines is that they are very easy to produce and store.

· Recombinant vector – by combining the physiology of one micro-organism and the DNA of another, immunity can be created against diseases that have complex infection processes. An example is the RVSV-ZEBOV vaccine licensed to Merck that is being used in 2018 to combat ebola in Congo.

· RNA vaccine is a novel type of vaccine which is composed of the nucleic acid RNA, packaged within a vector such as lipid nanoparticles. A number of RNA vaccines are under development to combat the COVID-19 pandemic.

· 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.[50]

· The use of plasmids has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, in human studies, this approach has failed to provide clinically relevant benefit. The overall efficacy of plasmid DNA immunization depends on increasing the plasmid's immunogenicity while also correcting for factors involved in the specific activation of immune effector cells.

While most vaccines are created using inactivated or attenuated compounds from micro-organisms, 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. A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms. The valency of a multivalent vaccine may be denoted with a Greek or Latin prefix (e.g., tetravalent or quadrivalent). In certain cases, a monovalent vaccine may be preferable for rapidly developing a strong immune response.

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 3 viruses in the vaccine. This phenomenon has also been found to be a problem with the dengue vaccines currently being researched.

Stages of Vaccine Development and Testing

Vaccine development and testing follow a standard set of steps. The first stages are exploratory in nature. Regulation and oversight increase as the candidate vaccine makes its way through the process.

Exploratory Stage

This stage involves basic laboratory research and often lasts 2-4 years. Federally funded academic and governmental scientists identify natural or synthetic antigens that might help

prevent or treat a disease. These antigens could include virus-like particles, weakened viruses or bacteria, weakened bacterial toxins, or other substances derived from pathogens.

Pre-Clinical Stage

Pre-clinical studies use tissue-culture or cell-culture systems and animal testing to assess the safety of the candidate vaccine and its immunogenicity, or ability to provoke an immune response. Animal subjects may include mice and monkeys. These studies give researchers an idea of the cellular responses they might expect in humans. They may also suggest a safe starting dose for the next phase of research as well as a safe method of administering the vaccine.

Researchers may adapt the candidate vaccine during the pre-clinical state to try to make it more effective. They may also do challenge studies with the animals, meaning that they vaccinate the animals and then try to infect them with the target pathogen.

Many candidate vaccines never progress beyond this stage because they fail to produce the desired immune response. The pre-clinical stages often lasts 1-2 years and usually involves researchers in private industry.

Next Steps: Clinical Studies with Human Subjects

Phase I Vaccine Trials

This first attempt to assess the candidate vaccine in humans involves a small group of adults, usually between 20-80 subjects. If the vaccine is intended for children, researchers will first test adults, and then gradually step down the age of the test subjects until they reach their target. Phase I trials may be non-blinded (also known as open-label in that the researchers and perhaps subjects know whether a vaccine or placebo is used).

The goals of Phase 1 testing are to assess the safety of the candidate vaccine and to determine the type and extent of immune response that the vaccine provokes. In a small minority of Phase 1 vaccine trials, researchers may use the challenge model, attempting to infect participants with the pathogen after the experimental group has been vaccinated. The participants in these studies are carefully monitored and conditions are carefully controlled. In some cases, an attenuated, or modified, version of the pathogen is used for the challenge.

A promising Phase 1 trial will progress to the next stage.

Phase II Vaccine Trials

A larger group of several hundred individuals participates in Phase II testing. Some of the individuals may belong to groups at risk of acquiring the disease. These trials are randomized and well controlled, and include a placebo group.

The goals of Phase II testing are to study the candidate vaccine’s safety, immunogenicity, proposed doses, schedule of immunizations, and method of delivery.

Phase III Vaccine Trials

Successful Phase II candidate vaccines move on to larger trials, involving thousands to tens of thousands of people. These Phase III tests are randomized and double blind and involve the experimental vaccine being tested against a placebo (the placebo may be a saline solution, a vaccine for another disease, or some other substance).

One Phase III goal is to assess vaccine safety in a large group of people. Certain rare side effects might not surface in the smaller groups of subjects tested in earlier phases.

Vaccine efficacy is tested as well. These factors might include 1) Does the candidate vaccine prevent disease? 2) Does it prevent infection with the pathogen? 3) Does it lead to production of antibodies or other types of immune responses related to the pathogen?