Vaccine

A vaccine is an antigenic preparation used to produce active immunity to a disease, in order to prevent or ameliorate the effects of infection by any natural or "wild" strain of the organism. 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 against cancer are also being investigated; see cancer vaccine. In this case, the antigenic preparation is derived from the cancer cell. There is also research on an HIV vaccine.

Origin of vaccines

Smallpox was the first disease people tried to prevent by purposely inoculating themselves with other types of infections. Inoculation is believed to have started in India or China before 200 BC. Physicians in China immunized patients by picking off pieces from drying pustules of a person suffering from a mild case of smallpox, grinding the scales to a powdery substance, and then inserting the powder into the person's nose in order for them to be immunized. In 1718, Lady Mary Wortley Montague reported that the Turks have a habit of deliberately inoculating themselves with fluid taken from mild cases of smallpox. Lady Montague inoculated her own children in this manner. In 1796, during the heyday of the smallpox virus in Europe, an English country doctor, Edward Jenner, observed that milkmaids would sometimes catch cowpox from dairy cows and were generally said to not then be able to catch smallpox. Cowpox is a mild relative of the deadly smallpox virus. Building on the foundational practice of inoculation, Jenner took infectious fluid from the hand of milkmaid Sarah Nelmes. He inserted this fluid, by scratching or injection, into the arm of a healthy local eight year old boy, James Phipps. Phipps then showed symptoms of cowpox infection. Forty-eight days later, after Phipps had fully recovered from cowpox, Jenner injected some smallpox-infected matter into Phipps, but Phipps did not later show signs of smallpox infection.

Types of vaccines

Vaccines may be living, weakened strains of viruses or bacteria which intentionally give rise to inapparent-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 which 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) causes 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 also 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.
• 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 and 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.

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.

Controversy surrounding the use of vaccines

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 UK 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. This outbreak was independent of the decline in uptake of MMR following the alleged misinformation generated by Wakefield's study (the age group affected were too old to have been due to receive the routine MMR immunisations around the time this article was published). The increase in cases of mumps in the UK instead relates to the age group affected being too young to have contracted natural mumps as a child (an effect of herd immunity due to the decline in mumps that followed the introduction of the MMR vaccine), but too old to have received the MMR vaccine. Individuals in this age group therefore had no immunity, either natural or vaccine induced, against mumps, and were susceptible to the re-emergence of this disease.[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 vaccination had been done. Parents were still able to refuse to vaccinate their children, but it involved completion of a statutory declaration after discussion with a doctor, and other bureaucracy. 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.

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. Thus 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 to the fetuses of pregnant women, but this risk can be effectively reduced by the immunization of children to prevent transmission to pregnant women.

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.

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.

Preservatives

In order to extend shelf life and reduce production and storage costs, thimerosal, a mercury-containing organic compound, was used routinely until recent years as a preservative. Thimerosal is gradually being phased out in the U.S. (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.

See also

• Immunology
• The Horse Named Jim

References

• AAPPublications.org - 'Thimerosal and the Occurrence of Autism: Negative Ecological Evidence From Danish Population-Based Data' Pediatrics, Vol 112, No 3, September 2003 (Denmark study on autism rates)
• BMJJournals.com - 'Comparative efficacy of three mumps vaccines', Matthias Schlegel, Joseph J. Osterwalder, Renato L. Galeazzi, Pietro J. Vernazza, British Medical Journal' Vol 319, No 352, August 7, 1999
• BrianDeer.com - 'Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children', Andrew Wakefield, et al., The Lancet, Vol 351, No 9103, February 28, 1998
• ColdCure.com - 'Zinc in the Treatment of Smallpox' (November 16, 2002)
• JPandS.org (pdf) - 'Thimerosal in Childhood Vaccines, Neurodevelopment Disorders, and Heart Disease in the United States', Mark Geier, M.D., Ph.D., and David Geier, B.A., Journal of American Physicians and Surgeons, Vol 8, No 1, Spring, 2003
• UNT.edu - Congressional Research Service (CRS) Reports regarding vaccines University of North Texas
• Vaccine Information.org - 'Vaccine Information for the Public and Health Professionals: Information about vaccine preventable diseases', Immunization Action Coalition
• SI.edu - 'History of Vaccines', Smithsonian Institute

External links

Vaccine proponent views

• CGDev.org -'Vaccines for Development' (updated regularly), Center for Global Development
• ClearlyExplained.com - 'Vaccines', Richard Conan-Davies, BSc Dip Ed (October 22, 2001)
• GlobalizationAndHealth.com - 'Medicines and vaccines for the world's poorest: Is there any prospect for public-private cooperation?'
• NIH.gov - 'Immunization' ('conventional' opinion on vaccines), National Institute of Health
• TownHall.com - 'Don't believe the childhood vaccine fearmongers', Michael Fumento (June 30, 2005)

Vaccine safety critical views

• MacroBiotic.net - 'A Short History of Vaccines'
• IOM.edu (pdf) - 'Before the Institute of Medicine' (statement on link between thimerosol and autism), US Congressman Dave Weldon, MD, (February 9, 2004)
• Liberty-Page.com - 'Bad Medicine: Or...How government interference in the vaccine market causes shortages, intellectual stagnation and death.'
• NoVaccine.com - 'The American Vaccine Information Directory' (AVID), Dr. Dan Schultz
• TruthCampaign.ukf.net - 'Vaccination Assault on the Human Species', Pat Rattigan, ND