Vaccine

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A vaccine is an antigenic preparation used to establish immunity to a disease. The term derives from Edward Jenner's use of cowpox ("vacca" means cow in Latin), which, when administered to humans, provided them protection against smallpox, which Pasteur and others perpetuated. The process of distributing and administrating vaccines is referred to as vaccination.

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).

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[edit] Types of vaccines

Avian Flu vaccine development by reverse genetics techniques.
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Avian Flu vaccine development by reverse genetics techniques.

Vaccines may be living, weakened strains of viruses or bacteria that intentionally give rise to unapparent-to-trivial infections. Vaccines may also be killed or inactivated organisms or purified products derived from them.

There are four types of traditional vaccines[1]:

  • Inactivated - these are previously virulent micro-organisms that have been killed with chemicals or heat. Examples are vaccines against flu, cholera, bubonic plague, and hepatitis A. Most such vaccines may have incomplete or short-lived immune responses and are likely to require booster shots.
  • Live, attenuated - these are live micro-organisms that have been cultivated under conditions that disable their virulent properties. They typically provoke more durable immunological responses and are the preferred type for healthy adults. Examples include yellow fever, measles, rubella, and mumps.
  • Toxoids - these are inactivated toxic compounds from micro-organisms in cases where these (rather than the micro-organism itself) cause illness. Examples of toxoid-based vaccines include tetanus and diphtheria.
  • Subunit - rather than introducing a whole inactivated or attenuated micro-organism to an immune system, a fragment of it can create an immune response. Characteristic example is the subunit vaccine against HBV that is composed of only the surface proteins of the virus (produced in yeast)

The live tuberculosis vaccine is not the contagious TB strain, but a related strain called "BCG"; it is used in the United States very infrequently.

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, but shows some promising results.

Note that 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.

[edit] 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 immune system is thus 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.

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 just 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. The difficulty of reaching all children, however, has caused the eradication date to be missed twice by 2006.

[edit] Vaccination schedule

Main article: Vaccination schedule

In order to provide best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines, with additional 'booster' shots often required to achieve 'full immunity'. This has led to the development of complex vaccination schedules. In the United States, the Advisory Committee on Immunization Practices, which recommends schedule additions for the Center for Disease Control, recommends routine vaccination of children against: hepatitis A, hepatitis B, polio, mumps, measles, rubella, diphtheria, pertussis, tetanus, HiB, chicken pox, rotavirus, influenza, meningococcal disease and pneumonia. The large number of vaccines and boosters recommended (up to 24 injections by age two) has led to problems with achieving full compliance. In order to combat declining compliance rates, various notification systems have been instituted and a number of combination injections are now marketed (e.g., Prevnar and ProQuad vaccines), which provide protection against multiple diseases.

A significant number of vaccinations may be a requirement for school admission at various grades. This requirement exists primarily to reduce the number of diseases which are transmissable in the classroom, not as comprehensive list of the vaccinations which may be appropriate for any given child. As a result, a school may require a vaccination for highly contagious diseases like HIB and chicken pox, which can cause significant school disruption during outbreaks, but is less likely to require vaccination against Hepatitis B, which is strictly a bloodborne pathogen and which can not be caught through the kind of casual contact one encounters in a classroom. In the US, individual states may set varying exemptions to compulsory vaccination that parents may claim for religious, ethical, or medical reasons.

Besides recommendations for infant vaccination boosters, many specific vaccines are recommended for repeated injections throughout life -- most commonly for measles, tetanus, influenza, and pneumonia. Pregnant women are often screened for continued resistance to rubella. In 2006, a vaccine was introduced against shingles, a disease caused by the chicken pox virus, which usually affects the elderly. Vaccine recommendations for the elderly concentrate on pneumonia and influenza, which are more deadly to that group.

[edit] Vaccine Controversies

Main article: Vaccine controversy

Opposition to vaccination, from a wide array of vaccine critics, has existed since the earliest vaccination campaigns: [2].

A number of vaccines, including those given to very young children, have contained thimerosal, a preservative that metabolizes into ethylmercury. It has been used in some influenza, DTP (diphtheria, tetanus and pertussis) vaccine formulations. Since 1997, use of thimerosal has been gradually diminishing in western industrialized countries after recommendations by medical authorities, but trace amounts of thimerosal remain in many vaccines and in some vaccines, thimerosal has not yet been phased out despite recommendations. Some states in USA have enacted laws banning the use of thimerosal in childhood vaccines.

In the late 1990s, controversy over vaccines escalated in both the US and the United Kingdom when a study, published in the respected journal Lancet, by Dr. Andrew Wakefield suggested a possible link between bowel disorders, autism and MMR vaccine, and urged further research [3]. His report, which focused upon a novel syndrome he described as autistic enterocolitis, garnered significant media attention, leading to a drop in the uptake of the MMR vaccine in the United Kingdom and some other countries. The study garnered criticism for its small sample size, and for failing to use healthy controls. In response to the controversies, a number of studies with larger sample sizes were conducted, and failed to confirm the findings.[4] [5]. In 2004, 10 of the 13 authors of the original Wakefield study retracted the paper's interpretation, without disputing the central finding of a consistent set of bowel disorders among the autistic study subjects, stating the data were insufficient to establish a causal link between MMR vaccine and autism.[6] Wakefield was also later found to have received a substantial sum from trial lawyers[7] to fund this research further calling into question the validity of its findings. Also in 2004, the United States' Institute of Medicine reported that evidence "favors rejection" of any link between vaccines containing thimerosal, or MMR, and the development of autism [8].

In 2004 and 2005, England and Wales experienced an increase in the incidence of mumps infections among adolescents and young adults. The age group affected were too old to have received the routine MMR immunisations around the time Wakefield et al's paper was published, and too young to have contracted natural mumps as a child, and thus to achieve a herd immunity effect. With the decline in mumps that followed the introduction of the MMR vaccine, these individuals had not been exposed to the disease, but still had no immunity, either natural or vaccine induced. Therefore, when the disease re-emerged as immunization rates declined following the controversy, they were susceptible to infection. [9][10]. This and similar examples indicate the importance of:

  1. careful modelling to anticipate the impact that an immunisation campaign will have on the epidemiology of the disease in the medium to long term
  2. ongoing surveillance for the relevant disease following introduction of a new vaccine and
  3. maintaining high immunisation rates, even when a disease has become rare.

There is opposition to vaccination (of any type) from some sectors of the community, particularly those who favour 'alternative' health care. Often this opposition is not based on specific data or details but rather a general leaning against conventional medicine and science. Naturopaths and other alternative health care practitioners sometimes offer their own, alternative treatments to conventional vaccination.

In Australia, a massive increase in vaccination rates was observed when the federal government made certain benefits (such as the universal 'Family Allowance' welfare payments for parents of children) dependent on vaccination. As well, children were not allowed into school unless they were either vaccinated or their parents completed a statutory declaration refusing to immunize them, after discussion with a doctor, and other bureaucracy. (Similar school-entry vaccination regulations have been in place in some parts of Canada for several years.) It became easier and cheaper to vaccinate one's children than not to. When faced with the annoyance, many more casual objectors simply gave in.

[edit] Potential for adverse side effects in general

Some refuse to immunize themselves or their children, because they believe certain vaccines' adverse side effects outweigh their benefits. A variation of this reasoning is that not enough is known of the adverse effects to determine whether the potential benefits make the risks worthwhile. Since most people are vaccinated against contagious and potentially fatal diseases, the chances of someone who is not vaccinated becoming ill is a good deal smaller than it might be if their opinion was held by more people. Therefore, they acquire some of the benefits of vaccines through herd immunity without assuming the risks those who choose to vaccinate do.

Advocates of recommended routine vaccination argue that side effects of most approved vaccines are either far less serious than actually catching the disease, or are very rare, and argue that the calculus of risk/benefit ratio should be based on benefit to humanity rather than simply on the benefit to the immunized individual. The main risk of rubella, for example, is serious birth defects, including autism (it is one of the very few known causes), in about one-quarter of fetuses of pregnant women who become infected. This risk can be effectively reduced by immunization during childhood to prevent transmission to pregnant women during later life. However, some parents specifically refuse to vaccinate their boys on the grounds that boys, after birth, do not suffer seriously if they catch this disease. Other people point out that these parents risk the health and well-being of their future grandchildren, since the unvaccinated male might, years later, catch this highly contagious disease and pass it along to his own pregnant wife, or any other pregnant woman.

[edit] Efficacy of vaccines

Vaccines do not guarantee complete protection from a disease. Even after a vaccination, there is still a possibility that a vaccinated person may get the disease. Sometimes this is because the host's immune system simply doesn't respond adequately or at all. This is known in medical jargon as a 'low titre of antibodies'. This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection) or just bad luck (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. Some germs can mutate (the common cold and influenza viruses are highly efficient at this), and in any case the immune system might still not be able to defeat the infection.

Adjuvants are typically used to boost immune response. 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) [11]
  • whether one kept to the timetable for the vaccinations (see Vaccination schedule)
  • 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

In cases where a vaccinated individual does develop the disease vaccinated against, the disease is likely to be milder than without vaccination.

[edit] Economics of vaccine development

One challenge in vaccine development is economic: many of the diseases most demanding a vaccine, including HIV, malaria and tuberculosis, exist principally in poor countries. Although some contend pharmaceutical firms and biotech companies have little incentive to develop vaccines for these diseases, because there is little revenue potential, the number of vaccines actually administered has risen dramatically in recent decades. This increase, particularly in the number of different vaccines administered to children before entry into schools may be due to government mandates, rather than economic incentive. Most vaccine development to date has relied on 'push' funding by government and non-profit organizations, of government agencies, universities and non-profit organizations.

Many researchers and policymakers are calling for a different approach, using 'pull' mechanisms to motivate industry. Mechanisms such as prizes, tax credits, or advance market commitments could ensure a financial return to firms that successfully developed an HIV vaccine. If the policy were well-designed, it might also ensure people have access to a vaccine if and when it is developed.

[edit] Preservatives

In order to extend shelf life and reduce production and storage costs, thimerosal, a preservative containing about 49% of a form of mercury called ethylmercury, was used routinely until recent years.[12] Thimerosal has been phased out in the U.S. in all but a few flu vaccines [13] (it has been phased out in other countries, e.g. Denmark in 1992), but may be used in stages of manufacture. Parents wishing to avoid this preservative, most common in multi-dose containers of influenza vaccine, may specifically ask for thimerosal-free alternatives that contain only trace amounts.[14] Recently, the Bush Administration has taken measures to drastically ease many regulations preventing mercury from being put into vaccines, and also has taken measures to permit industrial producers to use levels of mercury in vaccines much higher than previously permitted.[15]

[edit] List of Vaccines

GIDEON's vaccine list and vaccine trade name list

[edit] List of Vaccines Approved for Use in the United States

http://www.fda.gov/cber/vaccine/licvacc.htm

[edit] See also

[edit] References

    [edit] External links

    [edit] General

    [edit] Vaccine proponent views

    [edit] Vaccine safety critical views

    Vaccination/Vaccine (and Immunization, Inoculation. See also List of vaccine topics and Epidemiology)
    Development: Models - Timeline - Toxoid - Trial

    Administration: ACIP - GAVI - VAERS - Vaccination schedule - VSD

    Specific vaccines: Anthrax - BCG - Cancer - DPT - Flu - HIV - HPV - MMR - Pneumonia - Polio - Smallpox

    Controversy: A-CHAMP - Anti-vaccinationists - NCVIA - Pox party - Safe Minds - Simpsonwood - Thimerosal controversy - Vaccine injury

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