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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The pillars for the control of tuberculosis are early diagnosis&#44; appropriate treatment and prevention&#46; After the discovery of the bacteriologically based treatment of tuberculosis halfway through the last century&#44; various therapeutic regimens were established&#44; allowing us to cure the vast majority of patients&#46; However&#44; it must be said that very little progress has been made in this area in recent decades&#46; Prevention of tuberculosis remains focused on measures for avoiding contagion&#44; chemoprophylaxis and BCG vaccination&#46; Unlike the situation with other diseases such as smallpox&#44; poliomyelitis&#44; etc&#46;&#44; where vaccines have led to control and even&#44; in some cases&#44; eradication&#44; the role of the BCG vaccine has been constantly under discussion since it was introduced because&#44; in addition to interfering with the predictive value of the tuberculin test&#44; it has not managed to significantly modify the epidemiology of tuberculosis&#46; The efficacy of the vaccine is very variable &#40;0&#37;&#8211;80&#37;&#41;&#44; it does not prevent tuberculosis infection and it does not protect the infected patient&#46; The protection it does confer consists basically in preventing severe complications which may follow on from primary infection&#44; such as meningitis and miliary tuberculosis&#46; It is not recommended for systematic use in Spain&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite this&#44; we still believe that&#44; as has already occurred with other diseases&#44; an effective vaccine may be the right tool for achieving the anxiously awaited worldwide eradication of tuberculosis&#46; In this respect&#44; the discovery of the <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> genome and improved knowledge of the bacillus&#8217; immunopathology has opened new avenues of research into new vaccines for the prevention and treatment of tuberculosis&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Over the past 20 years&#44; enormous efforts and public and private financial resources have been poured into the search for and development of new vaccines in order to improve or replace the BCG&#46; Great progress has been made in the last 15 years that has produced a good number of vaccines now in the clinical development phase&#46; Furthermore&#44; various centers&#44; including some in Spain&#44; have specialized in the evaluation of candidate molecules in both animal models and in humans in clinical trial settings&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Existing candidate vaccines comprise the classic prophylactic and therapeutic vaccines&#46; Most vaccines are prophylactic&#44; and aim to prevent infection either by &#8220;priming&#8221; &#40;those that hope to replace the BCG&#41; or &#8220;boosting&#8221; &#40;those that improve BCG efficacy when both are administered in a combined regimen<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#41;&#46; Therapeutic vaccines are in the minority&#44; and are designed to prevent latent infection or the development of infection into disease or to reduce chemotherapy requirements&#46; The scant interest in these compounds probably dates from the time when widespread use of tuberculin in Europe as a treatment for tuberculosis caused severe side effects&#44; and the idea of a therapeutic vaccine against the disease was shelved&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Nevertheless&#44; a few success stories&#44; such as the RUTI vaccine that has obtained positive results in a phase 1 clinical trial and in another phase 2 study in subjects with and without HIV infection&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> have encouraged the scientific community to regard these strategies with less suspicion and even to include them among their short-term priorities&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">With regard to design&#44; candidate vaccines currently in clinical development are grouped into viral vector vaccines &#40;MVA85A&#44; AERAS-402&#44; AdAg85A&#41;&#44; proteins plus adjuvants &#40;M72&#44; Hybrid-1&#44; Hyvac-4&#44; H56&#41;&#44; recombinant BCG vaccines &#40;VPM 1002&#44; AERAS-422&#41; or dead bacillus extracts &#40;Mw&#44; RUTI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Producing vaccines is not an easy task&#44; at least not in the area of tuberculosis&#46; There are no biomarkers correlated with protection&#44; there is little consensus on the design of clinical trials and the sites capable of carrying them out&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and the selection and evaluation of new candidates needs to be rationalized&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5&#44;7</span></a> The ethical and regulatory requirements that accompany vaccine development can also cause problems&#46; As with all medications&#44; 15 years can elapse between design and marketing approval&#44; and the process is extremely costly&#46; Moreover&#44; experience with BCG in HIV-infected subjects and the introduction of genetically engineered vaccines call for extra efforts to guarantee vaccine safety&#44; an issue that has started to be addressed in regulatory guidelines<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and successfully implemented in research groups&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Initiatives such as the TBVAC and NEWTBVAC projects &#40;funded by the European Union Seventh Framework Program&#41; and the GC12 project from the Bill and Melinda Gates Foundation have fostered collaboration between the main players in the development of TB vaccines&#46; However&#44; there is still room for improvement in methodological harmonization and&#44; unfortunately&#44; an effective TB vaccine remains elusive&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The great hopes invested in TB vaccines faded when the most promising and outstanding candidate&#44; MVA85A&#44; was shown to be incapable of protecting against tuberculosis infection and disease in a clinical trial conducted in 2794 children in South Africa&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Yet the enormous effort made in recent years has not been in vain&#46; Knowledge of the disease and vaccine design and development has deepened considerably&#44; and a very high degree of international collaboration with a single common objective has been achieved&#46; However&#44; from now on&#44; vaccine strategies will have to be redesigned&#44; and the scientific community will have to be prepared to consider new less orthodox proposals&#44; such as therapeutic vaccines&#44; and proposals rejected long ago&#44; such as those focusing on humoral immunity&#44; may have to reexamined&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">It is safe to say that we have not yet achieved our dream of finding a really effective vaccine against tuberculosis&#44; but considering the pace of recent developments&#44; it is not unreasonable to believe that this may occur in the not too distant future&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ruiz Manzano J&#44; Vilaplana C&#46; &#191;Trataremos la tuberculosis con vacunas en el siglo <span class="elsevierStyleSmallCaps">xxi</span>&#63; Arch Bronconeumol&#46; 2014&#59;50&#58;373&#8211;374&#46;</p>"
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Editorial
Will We Be Treating Tuberculosis With Vaccines in the xxi Century?
¿Trataremos la tuberculosis con vacunas en el siglo xxi?
Juan Ruiz Manzanoa,
Corresponding author
jruiz@separ.es

Corresponding author.
, Cristina Vilaplanab
a Servicio de Neumología, Hospital Universitario Germans Trias y Pujol, Badalona, Departamento de Medicina de la Universidad Autónoma de Barcelona (UAB), CIBER de respiratorio (CIBERes), Spain
b Unitat de Tuberculosi Experimental, Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The pillars for the control of tuberculosis are early diagnosis&#44; appropriate treatment and prevention&#46; After the discovery of the bacteriologically based treatment of tuberculosis halfway through the last century&#44; various therapeutic regimens were established&#44; allowing us to cure the vast majority of patients&#46; However&#44; it must be said that very little progress has been made in this area in recent decades&#46; Prevention of tuberculosis remains focused on measures for avoiding contagion&#44; chemoprophylaxis and BCG vaccination&#46; Unlike the situation with other diseases such as smallpox&#44; poliomyelitis&#44; etc&#46;&#44; where vaccines have led to control and even&#44; in some cases&#44; eradication&#44; the role of the BCG vaccine has been constantly under discussion since it was introduced because&#44; in addition to interfering with the predictive value of the tuberculin test&#44; it has not managed to significantly modify the epidemiology of tuberculosis&#46; The efficacy of the vaccine is very variable &#40;0&#37;&#8211;80&#37;&#41;&#44; it does not prevent tuberculosis infection and it does not protect the infected patient&#46; The protection it does confer consists basically in preventing severe complications which may follow on from primary infection&#44; such as meningitis and miliary tuberculosis&#46; It is not recommended for systematic use in Spain&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite this&#44; we still believe that&#44; as has already occurred with other diseases&#44; an effective vaccine may be the right tool for achieving the anxiously awaited worldwide eradication of tuberculosis&#46; In this respect&#44; the discovery of the <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> genome and improved knowledge of the bacillus&#8217; immunopathology has opened new avenues of research into new vaccines for the prevention and treatment of tuberculosis&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Over the past 20 years&#44; enormous efforts and public and private financial resources have been poured into the search for and development of new vaccines in order to improve or replace the BCG&#46; Great progress has been made in the last 15 years that has produced a good number of vaccines now in the clinical development phase&#46; Furthermore&#44; various centers&#44; including some in Spain&#44; have specialized in the evaluation of candidate molecules in both animal models and in humans in clinical trial settings&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Existing candidate vaccines comprise the classic prophylactic and therapeutic vaccines&#46; Most vaccines are prophylactic&#44; and aim to prevent infection either by &#8220;priming&#8221; &#40;those that hope to replace the BCG&#41; or &#8220;boosting&#8221; &#40;those that improve BCG efficacy when both are administered in a combined regimen<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#41;&#46; Therapeutic vaccines are in the minority&#44; and are designed to prevent latent infection or the development of infection into disease or to reduce chemotherapy requirements&#46; The scant interest in these compounds probably dates from the time when widespread use of tuberculin in Europe as a treatment for tuberculosis caused severe side effects&#44; and the idea of a therapeutic vaccine against the disease was shelved&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Nevertheless&#44; a few success stories&#44; such as the RUTI vaccine that has obtained positive results in a phase 1 clinical trial and in another phase 2 study in subjects with and without HIV infection&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> have encouraged the scientific community to regard these strategies with less suspicion and even to include them among their short-term priorities&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">With regard to design&#44; candidate vaccines currently in clinical development are grouped into viral vector vaccines &#40;MVA85A&#44; AERAS-402&#44; AdAg85A&#41;&#44; proteins plus adjuvants &#40;M72&#44; Hybrid-1&#44; Hyvac-4&#44; H56&#41;&#44; recombinant BCG vaccines &#40;VPM 1002&#44; AERAS-422&#41; or dead bacillus extracts &#40;Mw&#44; RUTI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Producing vaccines is not an easy task&#44; at least not in the area of tuberculosis&#46; There are no biomarkers correlated with protection&#44; there is little consensus on the design of clinical trials and the sites capable of carrying them out&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and the selection and evaluation of new candidates needs to be rationalized&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5&#44;7</span></a> The ethical and regulatory requirements that accompany vaccine development can also cause problems&#46; As with all medications&#44; 15 years can elapse between design and marketing approval&#44; and the process is extremely costly&#46; Moreover&#44; experience with BCG in HIV-infected subjects and the introduction of genetically engineered vaccines call for extra efforts to guarantee vaccine safety&#44; an issue that has started to be addressed in regulatory guidelines<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and successfully implemented in research groups&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Initiatives such as the TBVAC and NEWTBVAC projects &#40;funded by the European Union Seventh Framework Program&#41; and the GC12 project from the Bill and Melinda Gates Foundation have fostered collaboration between the main players in the development of TB vaccines&#46; However&#44; there is still room for improvement in methodological harmonization and&#44; unfortunately&#44; an effective TB vaccine remains elusive&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The great hopes invested in TB vaccines faded when the most promising and outstanding candidate&#44; MVA85A&#44; was shown to be incapable of protecting against tuberculosis infection and disease in a clinical trial conducted in 2794 children in South Africa&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Yet the enormous effort made in recent years has not been in vain&#46; Knowledge of the disease and vaccine design and development has deepened considerably&#44; and a very high degree of international collaboration with a single common objective has been achieved&#46; However&#44; from now on&#44; vaccine strategies will have to be redesigned&#44; and the scientific community will have to be prepared to consider new less orthodox proposals&#44; such as therapeutic vaccines&#44; and proposals rejected long ago&#44; such as those focusing on humoral immunity&#44; may have to reexamined&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">It is safe to say that we have not yet achieved our dream of finding a really effective vaccine against tuberculosis&#44; but considering the pace of recent developments&#44; it is not unreasonable to believe that this may occur in the not too distant future&#46;</p></span>"
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Article information
ISSN: 15792129
Original language: English
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