“A vaccine is a biological preparation that establishes or improves immunity to a particular disease.”
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). The term vaccine derives from Edward Jenner’s 1796 use of the term cow pox (Latin variolæ vaccinæ, adapted from the Latin vaccÄ«n-us, from vacca cow), which, when administered to human, provided them protection against small pox.
The early vaccines were inspired by the concept of variolation originating in China, in which a person is deliberately infected with a weak form of smallpox as a form of inoculation. Jenner observed that milkmaid who had contact with cowpox did not get smallpox. He discovered that deliberate vaccination with cowpox (which has very mild effect in humans) would prevent smallpox (which is often fatal). Jenner’s work was continued by Louis Pasteur and others in the 19th century. The 19th and 20th centuries saw the introduction of several successful vaccines against a number of infectious diseases. These included bacterial and viral diseases, but not (to date) any parasitic diseases. Opposition to vaccination, from a wide array of vaccine critics, has existed since the earliest vaccination campaigns. Disputes have arisen over the morality, ethics, effectiveness, and safety of vaccination. The mainstream medical opinion is that the benefits of preventing suffering and death from serious infectious diseases greatly outweigh the risks of rare adverse effect following immunization. Some vaccination critics say that vaccines are ineffective against disease or that vaccine safety studies are inadequate. Some religious groups do not allow vaccination, and some political groups oppose mandatory vaccination on the grounds of individual liberty.
Types of Vaccines
There are four types of traditional vaccines:
- Dead microorganisms containing vaccines-Vaccines containing killed microorganisms – these are previously virulent micro-organisms which have been killed with chemicals or heat. Examples are vaccines against flu, cholera, bubonic plague and hepatitis A.
- Live-attenuated vaccines-Vaccines containing live-attenuated microorganisms – these are live micro-organisms that have been cultivated under conditions that disable their virulent properties or which use closely-related but less dangerous organisms to produce a broad immune response. They typically provoke more durable immunological responses and are the preferred type for healthy adults. Examples include yellow fever, measles, rubella and mumps. The live tuberculosis vaccine is not the contagious strain, but a related strain called “BCG”; it is used in the United States very infrequently.
- Toxoids – these are inactivated toxic compounds in cases where these (rather than the micro-organism itself) cause illness. Examples of toxoid-based vaccines include tetanus and diptheria. Not all toxoids are for micro-organisms; for example, Crotalis atrox toxoid is used to vaccinate dogs against rattlesnake bites.
- 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. Characteristic examples include the subunit vaccine against HBV that is composed of only the surface proteins of the virus (produced in yeast) and the virus like particle (VLP) vaccine against human papillomavirus (HPV) that is composed of the viral major capsid protein.
A number of innovative vaccines are also in development and in use:
- 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.
- 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, created from an infectious agent’s DNA called DNA vaccination, has been developed. It works by insertion (and expression, triggering immune system recognition) into human or animal cells, of viral or bacterial DNA. 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.
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.
MONOVALENT AND MULTIVALENT VACCINES
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.
In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune response.
Injections are now marketed (e.g. Pneumococcal conjugate vaccine and MMRV vaccine), which provide protection against multiple diseases.
Methods of administration
A vaccine administration may be
- By injection (intramuscular, intradermal, subcutaneous),
- By puncture,
- Transdermal or
Vaccines do not guarantee complete protection from a disease. Sometimes this is because the host’s immune system simply doesn’t respond adequately or at all. This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection) or because the host’s immune system does not have a B cell capable of generating antibodies to that antigen.
Even if the host develops antibodies, the human immune system is not perfect and in any case the immune system might still not be able to defeat the infection.
Adjuvants are typically used to boost immune response. Adjuvants are sometimes called the dirty little secret of vaccines in the scientific community, as not much is known about how adjuvants work. Most often aluminium adjuvants are used, but adjuvants like squalene are also used in some vaccines and more vaccines with squalene and phosphate adjuvants are being tested. The efficacy or performance of the vaccine is dependent on a number of factors:
- the disease itself (for some diseases vaccination performs better than for other diseases)
- the strain of vaccine (some vaccinations are for different strains of the disease)
- whether one kept to the timetable for the vaccinations
- some individuals are ‘non-responders’ to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly
- other factors such as ethnicity or genetic predisposition
When a vaccinated individual does develop the disease vaccinated against, the disease is likely to be milder than without vaccination.
The following are important considerations in the effectiveness of a vaccination program:
- careful modeling to anticipate the impact that an immunization campaign will have on the epidemiology of the disease in the medium to long term
- ongoing surveillance for the relevant disease following introduction of a new vaccine and
- Maintaining high immunization rates, even when a disease has become rare.
In 1958 there were 763,094 cases of measles and 552 deaths in the United States. With the help of new vaccines, the number of cases dropped to fewer than 150 per year (median of 56). In early 2008, there were 64 suspected cases of measles. 54 out of 64 infections were associated with importation from another country, although only 13% were actually acquired outside of the United States; 63 of these 64 individuals either had never been vaccinated against measles, or were uncertain whether they had been vaccinated.
Adjuvants and preservatives
Vaccines typically contain one or more adjuvants, used to boost the immune response. Tetanus toxoid, for instance, is usually adsorbed onto alum. This presents the antigen in such a way as to produce a greater action than the simple aqueous tetanus toxoid. People who get an excessive reaction to adsorbed tetanus toxoid may be given the simple vaccine when time for a booster occurs.
In the preparation for the 1990 Gulf campaign, Pertussis vaccine (not acellular) was used as an adjuvant for Anthrax vaccine. This produces a more rapid immune response than giving only the Anthrax, which is of some benefit if exposure might be imminent.
They may also contain preservatives, which are used to prevent contamination with bacteria or fungi. Until recent years, the preservative thiomersal was used in many vaccines that did not contain live virus. As of 2005, the only childhood vaccine in the U. S. that contains thiomersal in greater than trace amounts is the influenza vaccine, which is currently recommended only for children with certain risk factors. The UK is considering Influenza immunisation in children perhaps as soon as in 2006-7. Single-dose Influenza vaccines supplied in the UK do not list Thiomersal (its UK name) in the ingredients. Preservatives may be used at various stages of production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole.
Combined vaccinations are now widely used around the world, a result of the rapid increase in the number of shots recommended in current vaccination schedules.
The latest developments in vaccine delivery technologies have resulted in oral vaccines. A polio vaccine was developed and tested by volunteer vaccinations with no formal training; the results were very positive in that the ease of the vaccines increased dramatically. With an oral vaccine, there is no risk of blood contamination. Oral vaccines are likely to be solid which have proven to be more stable and less likely to freeze; this stability eliminates the need for a “cold chain”: the resources required to keep vaccines within a restricted temperature range from the manufacturing stage to the point of administration, which, in turn, will decrease costs of vaccines. Finally, a microneedle approach, which is still in stages of development, seems to be the vaccine of the future, the microneedle, which is “pointed projections fabricated into arrays that can create vaccine delivery pathways through the skin”.
Use in nonhumans
Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans. Both animals kept as pets and animals raised as livestock are routinely vaccinated. In some instances, wild populations may be vaccinated. This is sometimes accomplished with vaccine-laced food spread in a disease-prone area and has been used to attempt to control rabies in raccoons.
Where rabies occurs, rabies vaccination of dogs may be required by law. Other canine vaccines include canine distemper, canine parvovirus, infectious canine hepatitis, adenovirus-2 etc. among others.
Vaccine development has several trends:
- Until now, most vaccines have been aimed at infants and children, but adolescents and adults are increasingly being targeted.
- Combinations of vaccines are becoming more common; vaccines containing five or more components are used in many parts of the world.
- New methods of administering vaccines are being developed, such as skin patches, aerosols via inhalation devices, and eating genetically engineered plants.
- Vaccines are being designed to stimulate innate immune responses, as well as adaptive.
- Attempts are being made to develop vaccines to help cure chronic infections, as opposed to preventing disease.
- Vaccines are being developed to defend against bioterrorist attacks such as anthrax, plague, and smallpox.
Principles that govern the immune response can now be used in tailor-made vaccines against many noninfectious human diseases, such as cancers and autoimmune disorders. For example, the experimental vaccine CYT006-AngQb has been investigated as a possible treatment for high blood pressure.