[e-drug] Vaccines and vaccination

[Valeria Frighi <valeria.frighi@dtu.ox.ac.uk>]

E-drug: Vaccines and vaccination
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[Copied as fair use. For full article, go to the NEJM site. HH]

Review article

The New England Journal of Medicine
Vol.345, No.14 October 4, 2001. www.nejm.org

Vaccines and vaccination
Gordon Ada, D.Sc.

>From the John Curtin School for Medical Research, Australian
National University, Canberra, Australia. Address reprint requests to
Dr. Ada at the John Curtin School for Medical Research, Australian
National University, Box 334, ACT 2601 Canberra, Australia. 

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 the other bacteria
and viruses and about half of the parasites. Table 1 lists infections
for which there are now licensed vaccines and those for which a
candidate vaccine has undergone a phase 3 clinical trial, 2
indicating that a vaccine will probably be licensed within 5 to 10
years. 

Traditionally, attenuated vaccines were made by repeated passaging
of the infectious agent in tissue culture or animal hosts until its
virulence was greatly decreased but its immunogenicity was
retained. Alternatively, chemicals such as formalin were used to
destroy infectivity. More recently, parts of an infectious agent,
usually a surface antigen, have been used as a subunit vaccine. The
current vaccines against hepatitis B virus and Lyme disease rely on
recombinant-DNA technology. Bacterial toxins are rendered
nontoxic by chemical treatment, and the resulting toxoid protects
against the infectious agent. Protection against some types of
encapsulated bacteria has been achieved by immunization with a
capsular oligosaccharide or polysaccharide, but these T-cell
independent antigens induce only IgM antibodies, which are poorly
protective in infants. Conjugating this saccharide to a protein or
proteinaceous complex induces IgG antibodies because T cells
recognize the complex of a peptide with a
major-histocompatibility-complex molecule on the
antigen-presenting cell. The Haemophilus influenzae type b
conjugate vaccines also induce mucosal immunity, which reduces
nasal carriage of the bacteria. Such conjugates protect infants very
effectively.

....snip ....

Conclusions

The remarkable success of many vaccines, especially those
administered in childhood, and their impressive safety record,
together with the eradication of smallpox, are regarded among the
greatest public health achievements of the 20th century. But there
are still many serious diseases caused by pathogens that evade or
subvert control by a specific humoral or cell-mediated immune
response. An immunization protocol involving a prime boost
approach (usually DNA followed by a chimeric live virus vector)has
induced strong cytotoxic-T-cell responses that prevented persistent
infection in mice and monkeys after a challenge with HIV-1 and
other serious human pathogens, including Ebola virus and
plasmodium. The success of the current clinical trials of vaccination
against HIV-1 with the use of this protocol would signal a paradigm
shift in the development of vaccines. The sequencing of the
genome of many bacteria is also an important step forward. Efforts
to use vaccination and immunotherapeutic techniques to battle
noncommunicable diseases, especially cancer and Alzheimer's
disease, are also expanding our horizons. The achievements of the
21st century may be as spectacular as those of the 20th century. 

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