Vaccines and Vaccine Development

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Vaccines and Vaccine Development

Introduction

Vaccines, the introduction of a substance to create an immune response against a pathogen (disease-causing organism), have been responsible for great advances in public health since their advent in the late 1700s. Vaccines have greatly decreased the incidence of once-common diseases that caused innumerable deaths and huge public-health expenditures, not to mention terrible human suffering. Even diseases that were once universally fatal, such as rabies, are now averted with vaccines.

History and Research

Smallpox was a very serious disease in humans from its first recorded appearances in Europe and China in the third century AD until its eradication in the 1970s. The smallpox virus produced fever and headache, followed by a rash of pustules (small, pus-filled swellings), which gave the disease its name. In about 30% of cases, such severe damage was done to the skin or internal organs that death occurred. Even when the victims survived, they would often be badly scarred or even blinded by the ordeal.

Efforts to avoid infection with smallpox were early and widespread. Variolation, or intentional infection with smallpox, was prevalent because it was thought to produce a less virulent infection. This method was eventually recognized to be ineffective and even dangerous, leading to serious disease and deaths. At the end of the eighteenth century, Edward Jenner noticed that many milkmaids who had been infected with the cowpox virus did not contract smallpox. Jenner proved his theory by vaccinating a young boy with cowpox virus and then exposing him to smallpox. The vaccine was further developed into a stable and convenient dehydrated form in the 1950s.

The work of Louis Pasteur led to the germ theory of disease and the first vaccine for rabies. Later, the 1920s saw an increased number of inoculations for diseases such as diphtheria, pertussis (whooping cough), and tuberculosis, followed later by tetanus, yellow fever, polio, measles, mumps, and rubella. These familiar vaccinations, routinely given to children in the western world, markedly reduced incidences of these diseases. Expanded vaccination programs led to the goal of disease eradication, though to date only smallpox has been eliminated in natural settings.

Impacts and Issues

Despite the great advances in human health due to vaccines, controversy has arisen over their possible unintended effects, with the result of some parents choosing not to vaccinate their young children against disease. Indeed, different groups have opposed vaccination since the technique was developed. Early arguments were religious in nature, stating that God sent smallpox afflictions as punishment and thus to circumvent the disease was to thwart God's will. More recent objections have focused on a purported link between vaccines and serious conditions such as autism.

In 1998, Andrew Wakefield published a study in the journal Lancet that purported to link the MMR (measles, mumps, and rubella) vaccine with the development of bowel disease and autism. His appearance at a press conference fed a media frenzy that caused many concerned parents to reject the MMR vaccine specifically and sometimes vaccines in general. Subsequent reassurances by the medical establishment and politicians were disbelieved by so many United Kingdom parents that vaccination rates fell and outbreaks of disease were recorded. Though this hypothesis has not found support in many subsequent studies, distrust of the MMR vaccine has persisted; the United States Center for Disease control and Prevention has recommended the removal of the mercury-containing vaccine preservative Thimerosal, identified by anti-vaccinationists as a possible source of vaccine contamination, as a cautionary measure.

Vaccines are not, and have never been, without risk. Localized reactions, such as itching, swelling, pain, or discomfort are quite common, while systemic reactions, such as fever, headache, and malaise are less so. More seriously, illnesses such as encephalitis, dangerous seizures, unintentional infection with the target pathogen, and even death have occurred. The smallpox vaccine in particular, despite its long history, has been known to be comparatively more dangerous than other vaccines in use today. For this reason, only a small number of persons with specific occupations have been recommended for pre-exposure vaccination against smallpox, despite the concern about potential bio-terrorism attacks in the post-September-11th environment.

Regardless of these concerns, vaccines are still considered an important foundation of public health efforts around the world. The Center for Disease Control prudently considers it better to prevent a disease than to treat its symptoms. Though many once-fatal diseases can be successfully treated with today's advanced supportive care and antibiotics, the costs of vaccination are much lower than those of treating infection. Indeed, the National Institute of Allergy and Infectious Diseases cites a study stating that for each dollar spent on vaccinating against rubella, eight dollars are saved in costs that would have been spent treating the infection.

Two infectious disease outbreaks have created public interest in the quick development of therapeutic vaccines: the 2004 outbreak of SARS (Severe Acute Respiratory Syndrome) and the ongoing, low-intensity occurrences of H5N1 avian influenza, particularly in Asia. In the face of epidemics, however, mass vaccination is not always feasible and may present hazards to public health. Ring vaccination, or administering vaccine to populations within and immediately surrounding the outbreak, is an alternative measure used in many outbreaks of infectious disease. Similarly, development of vaccines is a long and complex process that requires great amounts of research and testing before vaccines become available.

Many different types of vaccines exist, some of which are easier to produce than others. Different types of vaccines produce varying degrees of resistance to disease, some requiring multiple doses or “booster shots” to remain effective. A great deal of study and preparation is required before work on a vaccine can begin. The life cycle of the pathogen, the way it functions and causes harm in the body, and the response of the immune system must all be examined before the most appropriate course of action can be determined.

WORDS TO KNOW

ATTENUATED STRAIN: A bacterium or virus that has been weakened, often used as the basis of a vaccine against the specific disease caused by the bacterium or virus.

RING VACCINATION: Ring vaccination is the vaccination of all susceptible people in an area surrounding a case of an infectious disease. Since vaccination makes people immune to the disease, the hope is that the disease will not spread from the known case to other people. Ring vaccination was used in eliminating the smallpox virus.

VARIOLATION: Variolation was the pre-modern practice of deliberately infecting a person with smallpox in order to make them immune to a more serious form of the disease. It was dangerous, but did confer immunity on survivors.

VACCINE TYPES

Vaccines with living, but weakened, viruses are termed attenuated vaccines. The attenuated virus does not cause a severe infection, but does present the body with sufficient challenge to mount and thus “learn” an immune response. MMR vaccines (the common abbreviation for the measles, mumps, and rubella vaccine) is an example of an attenuated vaccine.

Vaccination can also involve the use of dead viruses and bacteria. The antigen, usually a specific molecule that resides on the surface of the cell, is sufficient alone to provoke an immune response that subsequently provides protection against live bacteria or virus carrying the same surface molecule.

The third type of vaccination uses toxin produced by the living bacterium, but not the bacteria themselves. Diphtheria and tetanus vaccines are examples of toxoid vaccines promoted by the poster.

The fourth class of vaccine is engineered, or uses a chemical compound formed from the fusion of portions of two antigens. The Hib vaccine is such a biosynthetic vaccine.

Some types of vaccines are well understood, produce reliable immune responses, and are easy to produce. Many of these use attenuated (weakened but live) pathogens while others use dead organisms or portions of their proteins or antigens. Vaccines containing live, attenuated pathogens are not always appropriate for patients with weakened immune systems; likewise, vaccines containing dead pathogens often produce a weak or short-lived immune response. Newer, possibly more effective types of vaccines are being explored, including those that use parts of the pathogen's DNA to cause the body to produce “natural vaccine” on its own. Once a vaccine is developed, it must undergo the usual three phases of clinical trials to establish safety, dosage, and effectiveness, as well as a stringent licensing process and continued monitoring for safety and contamination. The length of this process means that new vaccines cannot always be quickly developed to meet an immediate need.

The risk of an epidemic must also be balanced with the real likelihood of adverse events associated with vaccinating large numbers of people in short periods of time. If mass vaccinations are required, the timing of the campaign can help the healthcare system deal with adverse events more successfully. By increasing the length of a vaccination campaign from two to ten days, fewer people will experience adverse events at the same time, reducing strain on doctors and hospitals. In cases of extreme shortage, vaccines such as smallpox can be diluted to much weaker solutions than their intended strength and still produce immunity in a portion of those vaccinated.

As a public health tool, vaccines are an inexpensive way to prevent serious disease before it develops and spreads. Health officials, individuals, and parents must maintain high levels of compliance to ensure protection against disease outbreak. At the same time, one must responsibly evaluate the risks of vaccines when faced with the outbreak of dangerous disease.

Primary Source Connection

The following newspaper article appeared in the The New York Times in 2004. It explains the economics of vaccine development from the drug manufacturers’ point of view. Mentioned in the article is a vaccine under development for shingles, a chickenpox-related virus, and the overall trend for more vaccines for adolescents and adults rather than children. In an update to the article, the vaccine for shingles was approved in May 2006 and is recommended by the Centers for Disease Control and Prevention for all adults over age sixty.

BIBLIOGRAPHY

Periodicals

Belongia, Edward A., and Allison L. Naleway.

“Smallpox Vaccine: The Good, the Bad, and the Ugly.” Clinical Medicine and Research 1, 2 (2003): 87-92.

Web Sites

Centers for Disease Control and Prevention. “Mercury and Vaccines (Thimerosal).” <http://www.cdc.gov/od/science/iso/concerns/thimerosal.htm> (accessed June 14, 2007).

McCulloch, J. Huston, and James R. Meginniss. Ohio State University. “A Statistical Model of Smallpox Vaccine Dilution.” May 17, 2002. <http://www.econ.ohio-state.edu/jhm/smallpox.htm> (accessed June 14, 2007).

National Institutes of Health, National Institute of Allergy and Infectious Diseases. “Understanding Vaccines.” July 2003. <http://www.niaid.nih.gov/publications/vaccine/pdf/undvacc.pdf> (accessed June 14, 2007).

White, Andrew Dickinson. A History of the Warfare of Science with Theology in Christendom. “Chapter X: Theological Opposition to Inoculation, Vaccination, and the Use of Anaesthetics.” <http://abob.libs.uga.edu/bobk/whitem10.html> (accessed June 14, 2007).

World Health Organization. “Vaccines” <http://www.who.int/topics/vaccines/en> (accessed June 14, 2007).

Kenneth LaPensee

Infectious Diseases: In Context