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An update on vaccines for tuberculosis – there is more to it than just waning of BCG efficacy with time

Scientific Institute of Public Health(WIV-ISP-Site Ukkel), Program Host-Pathogen Interactions, Service Immunology , 642, Engelandstraat, B-1180 Brussels , Belgium +32 2 373 33 70
Expert opinion on biological therapy (Impact Factor: 3.65). 09/2012; 12(12). DOI: 10.1517/14712598.2012.721768
Source: PubMed

ABSTRACT Introduction: Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. Areas covered: After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials. Expert opinion: It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.

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    • "Hence, attempts at manually creating these deletions are on. Recombinant BCG vaccines co-expressing other antigens from pathogens are also in clinical trials (35, 36). For cholera too, many endogenously produced live attenuated vaccines (Peru15 and Bengal15) are available as a traveler’s vaccine in different countries (37–39). "
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    • "Healthy donors may be carriers for S. aureus or C. albicans, but in some instances these agents may be the cause of human disease (e.g., in immunologically compromised individuals) (Gow et al., 2012; Otto, 2009). BCG is used as a vaccine in order to protect humans from childhood tuberculosis and is the standard of care for treatment of bladder cancer (NB: all donors received BCG vaccination) (Kawai et al., 2013; Romano and Huygen, 2012). L. rhamnosus is considered to be a transient inhabitant of humans and is present in some yogurt preparations (Borriello et al., 2003). "
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    • "These leading vaccines are all designed as preventive vaccines and have been demonstrated in preclinical animal models to give varying levels of protection against M.tb. challenge [2,6,7]. This includes the MVA85A vaccine that recently failed to confer protection in a phase 2B efficacy trial in BCG vaccinated infants [33], a target population where it is clear in hindsight that the animal data supporting the performance of MVA85A are very limited [34]. "
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