In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

Previously we have shown that Ag85B-ESAT-6 is a highly efficient vaccine against tuberculosis. However, because the ESAT-6 Ag is also an extremely valuable diagnostic reagent, finding a vaccine as effective as Ag85B-ESAT-6 that does not contain ESAT-6 is a high priority. Recently, we identified a novel protein expressed by Mycobacterium tuberculosis designated TB10.4. In most infected humans, TB10.4 is strongly recognized, raising interest in TB10.4 as a potential vaccine candidate and substitute for ESAT-6. We have now examined the vaccine potential of this protein and found that vaccination with TB10.4 induced a significant protection against tuberculosis. Fusing Ag85B to TB10.4 produced an even more effective vaccine, which induced protection against tuberculosis comparable to bacillus Calmette-Guérin vaccination and superior to the individual Ag components. Thus, Ag85B-TB10 represents a new promising vaccine candidate against tuberculosis. Furthermore, having now exchanged ESAT-6 for TB10.4, we show that ESAT-6, apart from being an excellent diagnostic reagent, can also be used as a reagent for monitoring vaccine efficacy. This may open a new way for monitoring vaccine efficacy in clinical trials.

Diagnosis of latentMycobacterium tuberculosis infection is considered essential for tuberculosis control but is hampered by the lack of specific reagents. We report that strong recognition of tuberculosis complex-specific antigen ESAT-6 by healthy household contacts of tuberculosis patients correlates with the subsequent development of active tuberculosis during a 2-year follow-up period.In the next year tuberculosis (TB) is expected to be responsible for more than 2 million deaths and up to 8 million new infections (11). Latently or subclinically infected individuals continually arise as new foci of infection, but the identification of infected individuals for treatment is extremely difficult, as it is based on intradermal injection of purified protein derivative (PPD). Unfortunately, PPD contains many antigens widely shared among mycobacteria, and the specificity of this reagent is therefore low. Several studies have demonstrated that PPD cannot reliably distinguish between previous Mycobacterium bovis BCG vaccination, exposure to environmental mycobacteria, or infection with M. tuberculosis (4,6,7). That the PPD skin test remains in use despite these limitations reveals the urgent need for better diagnostic tests for TB.Recently, genes which are deleted from BCG have been identified (2), and some of these also appear to be absent from most environmental mycobacteria. One such antigen, ESAT-6, has shown promising results for use as an immunodiagnostic reagent (1). Recent studies with humans have found that a test based on the detection of ESAT-6-specific T cells via their production of gamma interferon (IFN-␥) ex vivo specifically discriminates between M. tuberculosis infection and exposure to other mycobacteria (8,9,12).In the present study, healthy household contacts of sputumpositive TB patients were recruited from Hossana Regional Hospital, Hossanna, Ethiopia. The presence of active TB in all contacts at the time of entry into the study was excluded by radiological and clinical examinations and by sputum microscopy and culture, as described previously (5). Blood samples were obtained from all contacts at the time of entry into the study and were analyzed for in vitro responses to PPD and ESAT-6. The contacts were assessed again approximately 2 years after the first visit. On the second visit, the contacts received the same clinical and laboratory examinations for TB as they had previously.At follow-up, 12 of the 24 contacts (50%) were classified as "remaining healthy." They had no symptoms of TB and no lesions or other suspicious findings visible on X ray. Five of these contacts were sputum negative by microscopy and culture, while the remaining seven were unable to produce sputum.Of the remaining 12 contacts, 7 (29%) were found to have developed active TB on the basis of the presence of characteristic symptoms and findings on X rays (extensive infiltration of the lungs, calcification or lesions). For two of the contacts, the diagnosis of TB was confirmed by culture and/or microscopy, for one contact the r...

The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes “protective immunity” is one of the holy grails of M. tuberculosis immunology. It is known that IFN-γ is essential for protection, but it is also apparent that IFN-γ levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4δ2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response.

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