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Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) has variable efficacy in preventing tuberculosis. We hypothesized that some of this variation might be due to differences among BCG strains. To test this, neonates in Orizaba, Mexico, were vaccinated with one of three different BCG strains (BCG-Brazil It is estimated that approximately one-third of the world's population is infected with Mycobacterium tuberculosis, with 8 million new cases and nearly 3 million deaths occurring annually (30,38). Mycobacterium bovis bacille Calmete-Guérin (BCG), the most widely used vaccine in the world, is highly effective at reducing the risk of disseminated forms of tuberculosis in early childhood (11). However, studies have shown that its protection against adult tuberculosis is at best variable and often negligible (17). Variable BCG efficacy has been attributed to geographical differences (17), a masking effect due to an environmental mycobacterium (14), host genetic factors, or variations in BCG vaccine strains.Genomic analysis of BCG vaccines demonstrated that there are numerous genetic differences among the strains, including single-nucleotide polymorphisms, duplications, and deletions. The impact of these differences on the protective efficacy of BCG has not been determined. Functional studies comparing BCG immunogenicity and efficacy in laboratory animal models are subject to considerable controversy. In a mouse model, different BCG strains induced various levels of protection, with Japanese BCG (JBCG) unable to provide protection against mycobacterial challenge (7, 32). However, in a guinea pig model, both JBCG and Danish BCG (DBCG) provided good protection (43). In a recent study in Africa, vaccination with JBCG resulted in greater secretion of Th1 cytokines gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), and interleukin-2 (IL-2) than vaccination with DBCG (12).Central to the development of tuberculosis is the inability of M. tuberculosis-infected macrophages to contain the pathogen and the failure of T cells to confer long-lasting protective immunity. Therefore, the efficacy of BCG is associated with not only innate but also adaptive immune responses. In this study, we evaluated M. tuberculosis-specific recall immune response in infants vaccinated 1 year earlier with one of three BCG strains. After stimulation of peripheral blood mononuclear cells (PBMC) with culture filtrate proteins (CFP), mRNA for a panel of immune-related genes was monitored by quantitative real-time PCR. PBMC from children immunized with Brazilian BCG (BBCG) and DBCG expressed higher levels of IL-12␤, IL-27, and IFN-␥ in response to CFP, while those from children immunized with JBCG expressed higher levels of IL-1␣, IL-1␤, IL-6, and IL-24. MATERIALS AND METHODSParticipants. Healthy neonates were recruited at a community-based, general hospital in Veracruz, Mexico. Exclusion criteria for enrollment were birth weight below 2,500 g, a family history of tuberculosis, and known human immunodeficiency virus infection. In...

Kaposi’s sarcoma (KS) remains among the most common causes of oral cancer in HIV-infected individuals. Infection with the KS-associated herpesvirus (KSHV/HHV8) is a necessary event for disease development. Emerging evidence suggests that KSHV infects vascular endothelial (or endothelial progenitor) cells promoting the formation of the KS tumor (or spindle) cell. These cells elaborate angiogenic growth factors and cytokines that promote the dysregulated angiogenesis and profuse edema that characterizes this unusual vascular tumor. Central among these secreted factors is the potent endothelial cell mitogen, vascular endothelial growth factor (VEGF). Indeed, VEGF has proven to be a key player in KSHV pathogenesis and is a molecular hallmark of KS lesions. We have recently shown that a second angiogenic factor, Angiopoietin-like 4 (ANGPTL4), may also play a critical role in KS development. Here we demonstrate that ANGPTL4 is upregulated both directly and indirectly by the KSHV oncogene, vGPCR. We further show that ANGPTL4 is a molecular hallmark of oral KS lesions. Indeed, expression of this protein was observed in more tumor cells and in more biopsies specimens than expression of VEGF (23/25 or 92% vs. 19/25 or 76%, respectively) in oral KS. These surprising results support a key role for ANGPTL4 in Kaposi’s sarcomagenesis and further suggest that this angiogenic factor may provide a novel diagnostic and therapeutic marker for oral KS patients.