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.
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.
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
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).
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 ...