In H.G. Wells' classic novel The War of the Worlds, the invading, seemingly invincible Martians are rather quickly eliminated, not by the Earth's military, but by putrefactive and disease-producing bacteria and viruses?organisms that no longer plague earthlings.1 According to the author, a toll of a billion deaths has enabled earthlings to buy their birthright of immunity. Despite their advanced technology, the Martians were not equipped to deal with organisms that inhabit the Earth. They did not take the precaution of at least considering immunizations as part of their travel plans.
Humankind currently is faced with a similar threat that unfortunately is not based on fiction. This time it is from complacency along with emerging viruses and bacteria that are resistant to antibiotics. In the 1990s and even before, various reports signaled the dangers of excessive use of antibiotics in clinical practice. Now, the health care community is alarmed about "superbugs"?the drug-resistant bacteria taking hold in hospitals and in the community. Many researchers are predicting a return to the preantibiotic era, in which supportive treatment was one of the only options.
A recent large outbreak of mumps demonstrates that a percentage of people have not been vaccinated.2 There also have been recurrent cases of deadly viruses that plague third-world countries, and there is the possibility of the return of the deadly strain of influenza. Ebola, Hantaan, and Lassa viruses provoke the fear today that yellow fever, smallpox, and polio did in previous times. A type of avian influenza virus that killed more than 20 million persons between 1918 and 1919?more victims than died in World War I? may make a comeback.3
All of the above emphasizes greater need to find immunization methods to replace antibiotic therapy, as well as to urge individuals to become fully immunized with existing vaccines. Immunization has a long record of clinical success in preventing bacterial and viral diseases, and new methods presently are under study.
Recently, perceptions about the vaccines industry have shifted. Just a few years ago, companies were closing factories and leaving the business, all due to the complicated and costly manufacturing process and the low prices vaccines commanded in the market. As fears of new pandemics grow, however, and as new technologies promise to simplify vaccine making, the business has come back into vogue.4 There is much to consider when new vaccines are developed. This article will review the various types of vaccinations and current research.
Types of Vaccinations
More than 30 vaccines are licensed in the United States. There are several types of vaccines, including live virus or live bacteria; whole, killed virus or whole, killed bacteria; purified components (subunits) of virus or bacteria; and toxoids.5
Live Virus Vaccines
Live virus vaccines contain a harmless, attenuated strain of the wild, diseasecausing virus. The attenuated virus resembles the wild virus so closely that antibodies against the vaccine virus will crossprotect against the wild virus. Some common live virus vaccines are the measles, rubella, mumps, oral polio, and chickenpox vaccines.
Live Bacterial Vaccines
In the case of bacteria, which are more complex microbes than viruses, scientists have had less success in developing attenuated, harmless strains that can be used as vaccines. Live oral bacterial vaccines, however, elicit a strong immune response in the intestinal tract, and the immunity appears to be long-lasting. Live oral bacterial vaccines for typhoid fever and cholera are licensed abroad.
Whole, Killed Vaccines
The active ingredient in this type of vaccine is the whole, killed organism, which has a variety of surface and internal structures that are strong stimulants of the immune system. There is, however, an increased possibility of an allergic reaction. The microbe is inactivated by heat, phenol, formalin, or thimerosal. Unlike natural infection or live vaccine, killed vaccines require multiple doses initially to induce immunity, as well as booster doses later to maintain immunity. Anthrax, cholera, Japanese encephalitis, pertussis, plague, rabies, polio (inactivated type), and typhoid vaccines are examples.6
Purified vaccines consist of relatively pure chemical components of a microbe. Infectious agents have chemicals on their surface, some of which stimulate antibodies. In the case of bacteria, they are polysaccharides, a form of complex sugars. Viruses, on the other hand, usually are coated with proteins. In both cases, the vaccine is made by purifying these components by straightforward laboratory methods such as filtering, heating, and extracting with the appropriate solvents.
Purified vaccines are less likely to have side effects than whole virus vaccines. Their disadvantage is that they may require multiple doses and boosters to maintain immunity. Vaccines against hepatitis B, Haemophilus influenzae, and pneumococcal pneumonia are in this "purified" category.6
There is a concern, however, when developing vaccines for organisms that do not target all of the disease-causing serotypes. For example, the protein conjugate pneumococcal vaccine introduced in 2000 is derived from the 7 most commonly isolated pneumococcal serotypes, of which 90 are known to exist. The vaccine has proven to markedly reduce infections due to the vaccine strains in vaccine recipients. On the other hand, the vaccine also has been responsible for an increased prevalence of colonization and disease by nonvaccine strains.7
Toxoids produce antibodies against toxins secreted by certain bacteria, but not against the organism itself. To make a toxoid vaccine, the microbe is grown in large vats. The toxin it produces is extracted by filtration and other laboratory manipulations. Once the pure toxin has been prepared, it is incubated with formalin, producing the toxoid. When injected, the toxoid is nontoxic, but it stimulates antibodies that will combine with and so neutralize any subsequent exposure to the toxin. Common toxoid vaccines include those for diphtheria and tetanus.6
More than 70 bacteria, viruses, parasites, and fungi are serious human pathogens.Vaccines are available against some of these agents and are being developed against almost all of the other bacteria and viruses and about half of the parasites.5
The FDA recently announced approval of Merck's live oral rotavirus vaccine to prevent rotavirus gastroenteritis, a leading cause of severe diarrhea in infants and young children. Two other vaccines from the same company also have been approved. One is a cervical cancer treatment called Gardasil, which protects girls and women 9 to 26 years of age from diseases caused by human papillomavirus types 6, 11, 16, and 18. The other is Zostavax, for the prevention of herpes zoster.8,9 Zostavax is used for adults 60 years of age or older to prevent shingles.
An inactivated bacterial vaccine against leprosy is in phase 3 clinical trials, as are conjugated, subunit vaccines to prevent one form of meningitis and Staphylococcus aureus infections. Phase 3 trials also are ongoing for vaccines for Leishmania (a parasite) and Coccidioides (a fungus) infections.5 In addition, a phase 3 study is under way with a whole, killed vaccine for HIV, although the killing process may decrease its antigenicity.6
Intracel, a biopharmaceutical company, has just reached an agreement with the FDA on a pivotal study for a colon cancer vaccine. The product is a patient-specific tumor cell vaccine intended to treat stage II colon cancer after the tumor has been surgically removed. Moreover, for the first time an experimental vaccine against the deadly Marburg virus has shown efficacy in monkeys.10 Work also is being done to understand how long-term immunity works?which may lead to new ways of enhancing certain immune responses and to improving vaccines.11
Pharmacists no doubt will be asked about the new vaccines and the recommended immunization schedules for children and adults. Much of this information is available from the Centers for Disease Control and Prevention Web site.12 Patient information and labeling for recently approved vaccines can also be found by checking the FDA's internet address.9
Mr. Sherman is president of Sherman Consulting Services Inc.
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