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INTRODUCTION

Childhood immunizations represent one of the great public health achievements of the 20th and 21st centuries. According to the World Health Organization, immunization prevented at least 2 million child deaths in 2003 alone. Less than 250 years after Edward Jenner reported that inoculation with cowpox protected against smallpox, immunization against 15 different diseases before age 2 is routinely recommended in the United States. The individual, societal, and economic benefits of disease prevention resulting from the childhood and adult immunization programs in the United States are without question. A report from the Centers for Disease Control and Prevention (CDC) describing the benefits of vaccination of the 2009 birth cohort through 18 years of age estimated that 20 million cases of vaccine-preventable disease will not occur, 42,000 early deaths related to these diseases will be avoided, and $76 billion in direct and indirect costs will be averted. This economic benefit stands in stark contrast to the comparatively small cost for vaccine purchases. The estimated vaccine purchasing cost for a similar birth cohort based on 2015 pricing is $7.8 billion based on CDC cost and $11.6 billion at private sector pricing. The benefit from the reduction in suffering because of vaccine-preventable disease avoidance cannot be quantified.

IMMUNE RESPONSE

Many vaccines can be categorized as live or inactivated vaccines. Live vaccines contain organisms that have been attenuated or weakened so that the vaccine strain replicates in the host but rarely causes disease. The cowpox vaccine administered 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. In the 1940s, John Enders and his colleagues perfected viral culture techniques that enabled 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: the vaccine strains are derived from viral cultures co-infected with both human and bovine rotaviruses and contain genes from both “parent” viruses.

The immune response elicited by live attenuated vaccines is similar to that produced with natural infection. Live attenuated vaccines stimulate both humoral and cell-mediated immunity. Most live attenuated vaccines produce immunity in recipients after a single dose. Because a small number of recipients do not respond to the first dose of an injected live vaccine (such as measles, mumps, and rubella [MMR], or varicella), a second dose is recommended routinely to ensure a high level of immunity in the population (herd immunity). Although live attenuated vaccine strains replicate in the vaccinee, they usually do not cause disease such as may occur with the “wild” form of the organism. When a live attenuated vaccine does cause symptoms, it is ...

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