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Interventions for Tuberculosis Control and Elimination 2002

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this type of vaccine may not only protect against subsequent infection with<br />

M. tuberculosis, but may stimulate the immune response even among experimental<br />

animals with active disease. 1205 There are indications that the combination<br />

of priming with a DNA vaccine followed by a booster with BCG<br />

might induce higher protective efficacy in mice than BCG vaccination<br />

alone. 1206<br />

Recombinants<br />

Recombinant vaccines use existing microorganisms, e.g., vaccinia viruses 1207<br />

or BCG, 1208,1209 which are genetically modified to produce additional antigens<br />

thought to enhance the immune response. 1185 This approach is fairly<br />

recent <strong>and</strong> needs further research, which will most likely be aided by the<br />

deciphering of the entire sequence of the M. tuberculosis genome. 1210 In<br />

vitro, BCG engineered to secrete recombinant human interferon-alpha was<br />

substantially more active than unaltered BCG in inducing interferon gamma<br />

in human peripheral blood mononuclear cells 1209 In a guinea pig model,<br />

such a recombinant vaccine was superior than two BCG strains in preventing<br />

gross lesions <strong>and</strong> dissemination. 1211<br />

Subunits<br />

Particular components (subunits) of M. tuberculosis may be better suited to<br />

inducing protective immunity than an entire organism. Recent research is<br />

thus evaluating the protective efficacy of such subunits. 1212 Preliminary<br />

experimental studies appear to be promising, providing protection similar<br />

to that obtained with BCG vaccination. 1213,1214 Subunits are potentially specific<br />

<strong>and</strong> safe. A disadvantage of subunit vaccines is their limited persistence<br />

<strong>and</strong> thus potentially reduced duration of immune response. 1215 In<br />

experimental mice models, re-challenge with a mycloyl transferase protein<br />

significantly boosted the protection against challenge with M. tuberculosis<br />

in animals whose immune protection had waned following BCG vaccination<br />

at birth. 1216<br />

169

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