Editors' ChoiceIMMUNITY

Success May Require Being Direct

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Science Translational Medicine  30 Jan 2013:
Vol. 5, Issue 170, pp. 170ec19
DOI: 10.1126/scitranslmed.3005774

Finding successful strategies to minimize adverse effects while maximizing the effectiveness of a given treatment is a gold standard in drug design. Such approaches require smart but technologically feasible methods that can be combined with knowledge of disease to bring an effective product to the patients.

The design of vaccines against bacterial diseases such as tuberculosis provides a good example of the above. Tuberculosis is reemerging because of a combination of factors, including bacterial resistance to conventional treatments and the prevalence of disorders that weaken the immune system, such as malnutrition and infection with human immunodeficiency virus (HIV). The ability of Mycobacterium tuberculosis (MTB), the causative agent of this disease, to evade the host immune response has been a great challenge in the search for effective vaccine-design strategies. Bacille Calmette-Guérin (BCG) is a strain of M. bovis that is used as a vaccine to prevent MTB infection, but unfortunately it is only partially effective. Thus, the prevalence of tuberculosis remains high despite worldwide use of this immunization.

Waeckerle-Men and colleagues hypothesized that suboptimal immune responses to BCG vaccination may be attributable to an insufficient load of bacteria within the lymph nodes after the vaccine is administered into the skin. Microorganisms from body surfaces are normally collected in the lymph nodes, where they are recognized and killed, which then induces the immune response that helps prevent widespread infection. To test their hypothesis, the authors investigated whether direct injection of bacteria into the lymph nodes of mice would enhance the animals’ immune responses to BCG and to a subsequent rechallenge with MTB-purified protein derivative.

The results showed that indeed, direct delivery of BCG vaccine into the lymph nodes of mice stimulated the proliferation of lymphocytes and secretion of cytokines that contributed to the immune response against MTB proteins. The effectiveness of this technique in preventing active tuberculosis infection still needs to be confirmed, and the safety and feasibility of such an approach on a large scale in humans remain to be demonstrated. Nevertheless, the study provides important clues to advance the development of strategies for concentrating bacteria in the lymph nodes during immunization and potentially increasing the protective efficacy of the vaccine.

Y. Waeckerle-Men et al., Lymph node targeting of BCG vaccines amplifies CD4 and CD8 T-cell responses and protection against Mycobacterium tuberculosis. Vaccine, published online 25 December 2012 (10.1016/j.vaccine.2012.12.034). [Abstract]

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