chapter 18 caines HE DISCIPLINE OF IMMUNOLOGY HAS ITS ROOTS IN the early vaccination trials of Edward Jenner and Louis Pasteur. Since those pioneering efforts, vac cines have been developed for many diseases that were once major afflictions of mankind. The incidence of diseases such rubella(german measles), poliomyelitis, and tetanus has de clined dramatically as vaccination has become more com- mon. Clearly, vaccination is a cost-effective weapon for Vaccination with DNA disease prevention. Perhaps in no other case have the bene fits of vaccination been as dramatically evident as in the Active and Passive Immunization eradication of smallpox, one of mankind's long-standing and most terrible scourges. Since October 1977, not a single Designing Vaccines for Active Immunization naturally acquired smallpox case has been reported any- n Whole-Organism Vaccines where in the world. Equally encouraging is the predicted eradication of polio. The last recorded case of naturally ac- Purified Macromolecules as vaccines g Recombinant- Vector Vaccines 1991, and the World Health Organization(WHO) predicts that paralytic polio will be eradicated throughout the world DNA Vaccines within the next few years. A new addition to the weapons Multivalent Subunit vaccines gainst childhood disease is a vaccine against bacterial pneu- monia, a major cause of infant death a crying need remains for vaccines against other diseases Every year, millions throughout the world die from malaria, tuberculosis, and AIDS, diseases for which there are no effec- common usage. Experience has shown that not every vaccine tive vaccines. It is estimated by the World Health Organiza- candidate that was successful in laboratory and animal stud tion that 16,000 individuals a day, or 5.8 million a year, ies prevents disease in humans. Some potential vaccines become infected with HIv-1, the virus that causes AIDS. An cause unacceptable side effects, and some may even worsen effective vaccine could have an immense impact on the con- the disease they were meant to prevent. Live virus vaccines trol of this tragic spread of death and disaster. In addition to pose a special threat to those with primary or acquired im or thew enges presented by diseases for which no vaccines ex- munodeficiency(see Chapter 19). Stringent testing is an ist, there remains the need to improve the safety and efficacy solute necessity, because vaccines will be given to large of present vaccines and to find ways to lower their cost and numbers of well persons. Adverse side effects, even those that deliver them efficiently to all who need them, especially in de- occur at very low frequency, must be balanced against the po- loping countries of the world. The Who estimates that tential benefit of protection by the vaccine millions of infant deaths in the world are due to diseases that Vaccine development begins with basic research. Recent could be prevented by existing vaccines(see Clinical Focus). advances in immunology and molecular biology have led to The road to successful development of a vaccine that can effective new vaccines and to promising strategies for finding be approved for human use, manufactured at reasonable new vaccine candidates. Knowledge of the differences in epi cost, and efficiently delivered to at-risk populations is costly, topes recognized by t cells and B cells has enabled immuno ng, and tedious. Procedures for manufacture of materials ogists to begin to design vaccine candidates to maximize that can be tested in humans and the ways they are tested in activation of both arms of the immune system. As differences clinical trials are regulated closely. Even those candidate in antigen-processing pathways became evident, scientists cines that survive initial scrutiny and are approved for use in began to design vaccines and to use adjuvants that maximize human trials are not guaranteed to find their way into antigen presentation with class I or class II MHC molecules.common usage. Experience has shown that not every vaccine candidate that was successful in laboratory and animal stud￾ies prevents disease in humans. Some potential vaccines cause unacceptable side effects, and some may even worsen the disease they were meant to prevent. Live virus vaccines pose a special threat to those with primary or acquired im￾munodeficiency (see Chapter 19). Stringent testing is an ab￾solute necessity, because vaccines will be given to large numbers of well persons. Adverse side effects, even those that occur at very low frequency, must be balanced against the po￾tential benefit of protection by the vaccine. Vaccine development begins with basic research. Recent advances in immunology and molecular biology have led to effective new vaccines and to promising strategies for finding new vaccine candidates. Knowledge of the differences in epi￾topes recognized by T cells and B cells has enabled immunol￾ogists to begin to design vaccine candidates to maximize activation of both arms of the immune system. As differences in antigen-processing pathways became evident, scientists began to design vaccines and to use adjuvants that maximize antigen presentation with class I or class II MHC molecules. chapter 18 ■ Active and Passive Immunization ■ Designing Vaccines for Active Immunization ■ Whole-Organism Vaccines ■ Purified Macromolecules as Vaccines ■ Recombinant-Vector Vaccines ■ DNA Vaccines ■ Multivalent Subunit Vaccines Vaccines T        the early vaccination trials of Edward Jenner and Louis Pasteur. Since those pioneering efforts, vac￾cines have been developed for many diseases that were once major afflictions of mankind. The incidence of diseases such as diphtheria, measles, mumps, pertussis (whooping cough), rubella (German measles), poliomyelitis, and tetanus has de￾clined dramatically as vaccination has become more com￾mon. Clearly, vaccination is a cost-effective weapon for disease prevention. Perhaps in no other case have the bene￾fits of vaccination been as dramatically evident as in the eradication of smallpox, one of mankind’s long-standing and most terrible scourges. Since October 1977, not a single naturally acquired smallpox case has been reported any￾where in the world. Equally encouraging is the predicted eradication of polio. The last recorded case of naturally ac￾quired polio in the Western Hemisphere occurred in Peru in 1991, and the World Health Organization (WHO) predicts that paralytic polio will be eradicated throughout the world within the next few years. A new addition to the weapons against childhood disease is a vaccine against bacterial pneu￾monia, a major cause of infant death. A crying need remains for vaccines against other diseases. Every year, millions throughout the world die from malaria, tuberculosis, and AIDS, diseases for which there are no effec￾tive vaccines. It is estimated by the World Health Organiza￾tion that 16,000 individuals a day, or 5.8 million a year, become infected with HIV-1, the virus that causes AIDS. An effective vaccine could have an immense impact on the con￾trol of this tragic spread of death and disaster. In addition to the challenges presented by diseases for which no vaccines ex￾ist, there remains the need to improve the safety and efficacy of present vaccines and to find ways to lower their cost and deliver them efficiently to all who need them, especially in de￾veloping countries of the world. The WHO estimates that millions of infant deaths in the world are due to diseases that could be prevented by existing vaccines (see Clinical Focus). The road to successful development of a vaccine that can be approved for human use, manufactured at reasonable cost, and efficiently delivered to at-risk populations is costly, long, and tedious. Procedures for manufacture of materials that can be tested in humans and the ways they are tested in clinical trials are regulated closely. Even those candidate vac￾cines that survive initial scrutiny and are approved for use in human trials are not guaranteed to find their way into Vaccination with DNA