What is a Vaccine?

A vaccine is a biological suspension of weakened or killed pathogens or their components. It can be purified protein subunits, conjugated and nonconjugated polysaccharides, or split virions. The pathogen is usually a bacterium or a virus.

Vaccines can be delivered as a nasal spray, orally, or by injection. Humans become immune to microbial antigens through artificial and natural means. The immune system of the body must recognize the pathogen and be able to develop a defense against a specific pathogen.

The goal of administering vaccines, vaccination, is to produce artificially acquired, active immunity to a specific disease. Of all the public health measures against infections, administering a vaccine is the most cost-effective strategy.

Characteristics of a Vaccine

The purpose of a vaccine is to stimulate active immunity and create an immune memory so that exposure to the active disease microorganism will stimulate an already primed immune system to fight the disease. Most vaccines can be divided into the following two types:

Traditionally prepared vaccines are preparations of inactivated (killed) or live attenuated (weakened) bacteria or viruses, parts of the microorganisms, or toxoids (inactivated toxins) from the disease-causing agent. Newer synthetic vaccines use subunit vaccines, conjugate vaccines, and naked DNA vaccines. Critical to the protective effect of subunit vaccines (vaccines consisting of components of the pathogens) are additives called adjuvants, which amplify the immune response. Currently, an aluminum salt-based substance called alum and an oil-based substance called MF59 are two adjuvants licensed for clinical use.

Host Response to Vaccination

Classic preventive vaccines are designed to mimic the effects of natural exposure to microbes. The earliest host response to vaccination is called the innate immune response. This response is an evolutionarily ancient system of host defense that occurs within minutes or hours after vaccination. The dendritic cell is critical to this response. Dendritic cells can sense components of bacteria, viruses, parasites, and fungi through pathogen recognition receptors. One class of these receptors is the toll-like receptor (TLR); at least 10 have been described. As a group, TLRs can sense a wide variety of microbial stimuli (e.g., lipopolysaccharides, viral or bacterial DNA).

The intracellular TLR signaling within dendritic cells is mediated by at least four adapter proteins. Once dendritic cells decode and integrate the signals generated by sensing microbial molecules with TLRs, the cells convey this information to naïve antigen-specific T cells, which launch an immune response.

Over time, vaccine-induced immunity wanes; this may result in increased susceptibility later in life (e.g., varicella [shingles]). A second dose of vaccine could improve protection from primary vaccine failure and waning vaccine-induced immunity.

History of Vaccines

According to the World Health Organization (WHO), immunization is one of the greatest breakthroughs in medical science. This practice saves 3 million lives a year. Vaccines have reduced some preventable infectious diseases to an all-time low; few people now experience the devastating effects of measles, pertussis, and other infectious diseases.

The history of vaccination begins as early as 1000 bce, when the Chinese used smallpox inoculation or variolation, a method of scratching the skin and applying pulverized powder from a smallpox scab. By the 18th century, the practice of variolation became known to Europeans and Americans.

In 1796, Edward Jenner, an English physician, used cowpox scabs to create immunity to smallpox. This was a fundamental principle of immunization, which evolved over 200 years ago and has resulted in the eradication of smallpox globally. The first vaccine for chicken cholera was created in the laboratory of Louis Pasteur in 1879. In 1885, Pasteur developed a rabies vaccine. This launched a period of productive development of many other vaccines (e.g., diphtheria, tetanus, typhoid fever).

Applications of Vaccines

The concept of vaccination, or deliberately introducing a potentially harmful microbe into a patient, initially met with suspicion and outrage. Widespread vaccination programs against contagious infectious diseases now have a positive influence worldwide.

In 1721, Cotton Mather, a Boston minister, encouraged smallpox variolation as a preventive step subsequent to the Boston smallpox epidemic. Mather was widely criticized by suspicious citizens for his role in promoting variolation. Since the introduction of the first vaccine, there has been opposition to vaccination. In 1910, Sir William Osler expressed his frustration with the antivaccinationist movement. Although fear and mistrust have arisen every time a new vaccine was introduced in the 18th century, the antivaccine movement receded between the 1940s and the early 1980s. Three trends promoted a positive attitude toward vaccines:

An increase in antivaccinationist thinking emerged in the 1970s, when outbreaks of infectious diseases decreased, with more vaccines in the childhood vaccination schedule. When countries dropped pertussis vaccination from the vaccination schedule, the incidence of whooping cough increased 10 to 100 times. Fears grew in the late 1990s, when vaccines were suspected of causing autism. Once again, in 2009 and 2010, the H1N1 influenza pandemic evoked strong public fear of vaccination. Reemergence of a previously controlled disease, such as pertussis, has led to hospitalizations and deaths. The worst pertussis outbreaks in the past 50 years are now occurring in California.

Despite public fears, American children now receive vaccinations to numerous diseases that were once common childhood infectious diseases. In the United States, the recommended childhood immunization schedule now includes vaccines to protect against 15 diseases, including seasonal influenza. Immunization schedules vary by age and by country (Tables 16-1 to 16-3, A and B).

The latest adult immunization rates in the United States lag behind target levels. The Centers for Disease Control and Prevention (CDC) has reported that in 2010, the pneumococcal vaccination rate for patients at high risk was less than 20%. The hepatitis B vaccination rate for health care personnel was about 60%. In addition, the human papillomavirus (HPV) vaccination rate among young women was slightly more than 20%.

Adults require updates of certain vaccinations (Fig. 16-1). Especially serious diseases for adults age 65 years and older include diphtheria, herpes zoster (shingles), influenza, pneumococcus, and tetanus (lockjaw). In 2006, a vaccine was approved for adults older than 60 years to reduce the risk of shingles (reactivation of varicella virus) in those who had chickenpox in childhood. International travelers frequently require vaccination to endemic diseases in a particular country (e.g., hepatitis A, yellow fever). Health care professionals are now protected against hepatitis B by vaccines. Also, each year, many adults prepare for winter and the flu season by receiving flu vaccine.

The use of vaccines has spread to pets and livestock as well (e.g., rabies, Lyme disease, feline leukemia).

The safety of vaccines is a controversial public health issue because vaccines are in a unique niche in the marketplace. No vaccine is totally effective or 100% safe. The same components that make them effective may also cause serious adverse effects. It may not be possible to develop safer versions of vaccines without losing essential function.

In 1986, Congress enacted the National Childhood Vaccine Injury Act (NCVIA) to establish a no-fault compensation system for children who were harmed by adverse events following the administration of a vaccine if there was evidence that the vaccine actually caused the problem. Monitoring programs, such as the Vaccine Adverse Events Reporting System (VAERS) and the Clinical Immunization Safety Assessment Network, are essential to ensure tracking of actual but rare adverse events that may be related to vaccination. In 2011, the U.S. Supreme Court ruled that vaccine makers are immune from lawsuits alleging that the design of a vaccine is defective. Many physicians and public health organizations support this ruling because they believe that it will ensure the availability and promote the use of childhood vaccines. Current vaccines are considered safer and more protective than early products.

A U.S. Food and Drug Administration (FDA)–approved vaccine (Table 16-4) must meet specific requirements, as follows:

Inactivated vaccines are stored in powdered form and are reconstituted before administration. Live attenuated vaccines require refrigeration.

The Center for Biologics Evaluation and Research (CBER) regulates vaccine products. Many of these are childhood vaccines that have contributed to a significant reduction of vaccine-preventable diseases. According to the CDC, vaccines have reduced preventable infectious diseases to an all-time low and few people now experience the devastating effects of measles, pertussis, and other illnesses.

Vaccine development is an important focus of research related to acquired immunodeficiency syndrome (AIDS), malaria, and other devastating diseases. Recently recommended vaccines include a new measles-mumps-rubella-varicella vaccine for 1-year-old children and a tetanus-diphtheria-pertussis vaccine for people age 11 to 65 years.

Concerns About Vaccines

Vaccination requirements, even well-accepted laws on so-called classic childhood diseases (e.g., polio, measles, pertussis), have been resisted in recent years based on philosophical, political, scientific, and ideologic issues. In the past 20 years, the number of recommended pediatric vaccines has increased dramatically, despite unproven theories alleging connections between vaccines and illnesses, including autism, diabetes, and multiple sclerosis. An estimated 1% to 3% of U.S. children are excused by their parents from vaccine requirements, with rates as high as 15% to 20% in a few communities.

A vaccine for hepatitis E virus (HEV) vaccine has raised ethical concerns in Nepal. Testing the recombinant protein (rHEV) vaccine in a civilian population led to concerns that residents might not have access to the vaccines after the clinical trials concluded. Hepatitis E is common (endemic) in Nepal.

Representative Vaccines

Many different vaccines are currently available. Some emphasize public health safety (e.g., anthrax) and others prevent the return of epidemic diseases.

Vaccines in Biodefense

In regard to bioterrorism, the goal of the FDA is to foster the development of vaccines. Many products (e.g., FDA-regulated vaccines) could be affected by bioterrorism. Pathogens or pathogen products adapted for biological warfare include the following:

This determines IgG antibodies produced in response to vaccination by the method of quantitative multianalyte fluorescent detection.

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