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Childhood immunizations represent one of the great public health achievements of the 20th and 21st centuries.1According to the World Health Organization, immunization prevented at least 2 million child deaths in 2003 alone.2 Less than 250 years after Edward Jenner discovered that inoculation with cowpox protected against smallpox, immunization against 14 different diseases before age 2 is routinely recommended in the United States.

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Vaccines can be broadly categorized as live or inactivated vaccines. Live vaccines contain organisms that have been attenuated or weakened. They replicate in the host, simulating natural infection, but they rarely cause disease. The cowpox vaccine given by Jenner in 1796 to prevent smallpox is an example of a live vaccine. In the late 19th century, Louis Pasteur and others discovered methods to attenuate both viruses and bacteria through chemical means, leading to the development of early vaccines for anthrax and rabies. In the 1940s, John Enders and his colleagues perfected viral culture techniques that permitted the attenuation of viruses through serial passage in cell culture, paving the way for vaccines against polio, measles, mumps, and rubella. Some of the newest live vaccines are the products of genetic engineering. For example, one available rotavirus vaccine is produced by reassortment. Vaccine virus is derived from viral culture co-infected with both human and bovine rotaviruses and contains genes from both “parent” viruses.

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The immune response elicited by live attenuated vaccines is nearly identical to that produced after natural infection. Live attenuated vaccines stimulate both humoral and cell-mediated immunity. Some live attenuated vaccines are effective after a single dose and, in general, immunity after immunization with a live vaccine is long-lasting.3 Preexisting antibody to a live attenuated vaccine antigen, such a persisting transplacental maternal antibody in an infant, may interfere with replication of the vaccine virus in the vaccinee and prevent the development of an immune response. Rarely, live attenuated vaccines cause severe or fatal reactions as a result of uncontrolled replication in immunocompromised hosts.

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Inactivated vaccines may be produced from killed or inactivated whole bacteria (eg, the pertussis component of diphtheria–tetanus–whole cell pertussis vaccine, or DTwP) or viruses, or purified fractions of bacteria or viruses. Fractional vaccines may be protein or polysaccharide based. Protein-based vaccines include inactivated bacterial toxins called toxoids (the basis of diphtheria and tetanus vaccines) and subvirion or subunit products (inactivated influenza vaccine).

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Polysaccharide-based vaccines containing pure bacterial cell wall polysaccharide include early vaccines for the prevention of disease caused by Haemophilus influenzae type B (Hib),Streptococcus pneumoniae, and Neisseria meningitidis. Because polysaccharide antigens are T-cell-independent antigens, they are poorly immunogenic in children younger than age 2 and do not elicit immune memory in older children and adults. Conjugation of bacterial capsular polysaccharide to a protein carrier changes the immune response elicited by the vaccine antigen to a T-cell-dependent process, thus improving immunogenicity in young children and evoking immunologic memory. Polysaccharide-protein conjugate vaccines for the prevention of ...

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