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Probiotics are living microorganisms (e.g., bacteria) that are either the same as or similar to organisms found naturally in the human body and may be beneficial to health. Current researches have shown that the balance between beneficial and pathogenic bacteria is essential in order to maintain the oral health. Therefore, oral cavity has recently been suggested as a relevant target for probiotic applications. Dental caries can be seen as a microbial imbalance where the oral microbiota shift towards community dominance which produces acidogenic and acid-tolerant gram positive bacteria. Similarly, the accumulation of bacteria within the biofilm, facilitated by poor oral hygiene, predisposes to allogenic shifts in the microbial community, leading to the onset of periodontal inflammation. Probiotic bacteria belonging to the genus of Lactobacillus, Bifidobacterium and Streptococcus have been proven effective for preventing caries by reducing the number of cariogenic bacteria in saliva after a short period of consuming the probiotic. In contrast, the effect of probiotics on improving gingivitis and periodontitis has been less investigated. The currently available studies on the effect of probiotics on periodontal pathogens and clinical periodontal parameters showed differing results depending on the strains used and the endpoints analyzed. Many of the clinical studies are pilot in nature and with low quality, therefore, properly conducted clinical trials, using probiotic strains with in vitro proven periodontal probiotic effects, are needed. The putative beneficial effects of probiotics on oral malodour have also been evaluated, but further evidence is needed to fully explore the potential of probiotics for preventing malodour.

Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10–secreting type 1 regulatory T cells (Tr1) derived from Ag-stimulated T cells, which regulate inflammation-dependent adaptive immunity and minimize immunopathology. We establish herein that cell contact-mediated nTreg regulatory function is inhibited by inflammation, especially in the presence of the complement C3b receptor (CD46). Instead, as with other T-cell subsets, the latter inflammatory conditions of stimulation skew nTreg differentiation to Tr1 cells secreting IL-10, an effect potentiated by IFN-α. The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-α and that these immune components of inflammation are directly associated with active lupus. These results provide a rationale for using anti–IFN-α Ab immunotherapy in lupus patients.

International audience; Tumor growth depends on blood supply, requiring the development of new vessels, and vascular endothelial growth factor (VEGF) plays a central role in neoangiogenic processes. For this reason, VEGF represents a target for the development of new therapeutic antiangiogenic molecules. Clinical trials using anti-VEGF mAbs such as bevacizumab have validated the efficacy of this therapeutic approach but have also revealed adverse effects. Here we report that a VEGF-derived immunogen, consisting of a heterocomplex of a murine (m)VEGF and keyhole limpet hemocyanin, called "mVEGF kinoid," triggered a strong Ab immune response in mice. The anti-VEGF Abs inhibited both the proliferation of human umbilical vein endothelial cells cultured in the presence of mVEGF and the binding of mVEGF to its receptor-2 Flk-1. In mVEGF kinoid-immunized BALB/c mice challenged with syngeneic CT26 colorectal tumor cells, the number and size of lung metastases were significantly decreased. In human (h)VEGF kinoid-immunized BALB/c mice, high levels of serum Abs to hVEGF were present, and purified IgG from these mice decreased by > or =50% the tumor growth of human A673 rhabdomyosarcoma cells and HT29 colon carcinoma xenografted in Swiss nude and NOD/SCID mice, respectively. Tumor cell growth inhibition was similar to that observed in mice receiving therapeutic doses of bevacizumab. These experiments suggest that a therapeutic vaccine containing VEGF kinoid may represent a strategy for safely combating VEGF-dependent neovascularization and metastases occurring in malignant tumors.

The proinflammatory cytokine TNFalpha is a potent mediator of septic shock and a therapeutic target for chronic inflammatory pathologies including rheumatoid arthritis and Crohn's disease. As an alternative to anti-human TNFalpha (hTNFalpha) mAbs and other hTNFalpha blocker approved drugs, we developed an active anti-hTNFalpha immunotherapy, based on a vaccine comprised of a keyhole limpet hemocyanin-hTNFalpha heterocomplex immunogen (hTNFalpha kinoid) adjuvanted in incomplete Freund's adjuvant. In mice transgenic for hTNFalpha (TTg mice), hTNFalpha kinoid vaccination elicited high titers of Abs that neutralized hTNFalpha bioactivities but did not result in a cellular response to hTNFalpha. The vaccine was safe and effective in two experimental models. Kinoid-immunized but not control TTg mice resisted hTNFalpha-driven shock in one model and were prevented from spontaneous arthritis, inflammatory synovitis, and articular destruction in a second model. These data demonstrate an anti-cytokine induction of autoimmune protection against both acute and chronic hTNFalpha exposure. They show that active vaccination against a human cytokine can be achieved, and that the immune response can be effective and safe.

The Tat protein is essential for HIV type 1 (HIV-1) replication and may be an important virulence factor in vivo . We studied the role of Tat in viral pathogenesis by immunizing rhesus macaques with chemically inactivated Tat toxoid and challenging these animals by intrarectal inoculation with the simian/human immunodeficiency virus 89.6PD. Immune animals had significantly attenuated disease with lowered viral RNA, interferon-α, and chemokine receptor expression (CXCR4 and CCR5) on CD4 + T cells; these features of infection have been linked to in vitro effects of Tat and respond similarly to extracellular Tat protein produced during infection. Immunization with Tat toxoid inhibits key steps in viral pathogenesis and should be included in therapeutic or preventive HIV-1 vaccines.

Anti-Tat therapeutic vaccination has been clinically investigated by different groups [1-4], given that 1) extracellular Tat protein induces T cell apoptosis and cellular immune suppression, 2) epidemiological data showed that LTNP exhibit high level of serum anti-Tat Ab, negatively correlated with p24 antigenemia, 3) in Tat immunized macaques, viremia decreased following SHIV challenge. Anti-Tat therapeutic vaccination using Tat Toxoid adjuvanted either with Seppic [1,2] or with alum or DcChol (Aventis Pasteur) proved to be safe. A prospective structured treatment interruption study (STI) monitored according to EU guidelines was conducted at Hospital St-Pierre, Brussels (Pr. N. Clumeck) on 31 vaccinees who received a DcChol adjuvanted Tat Toxoid (n = 12), a DcChol placebo (n = 8) or non adjuvanted Tat toxoid (n = 11). The 2 year study follow-up showed that vaccinees developing high titer of Abs neutralizing Tat bioactivity prolonged HAART-interruption., info:eu-repo/semantics/published, Oral presentation. From 2006 International Meeting of The Institute of Human VirologyBaltimore, USA. 17–21 November, 2006

O tratamento de infecções crônicas recidivantes (I.C.R.) encontra muitas dificuldades. No presente estudo, o uso do imunoadjuvante P40, quer isolado, quer associado a vacinoterapia no tratamento de I.C.R., demonstrou ser muito eficaz, ao passo que a vacinoterapia isoladamente não o foi. Foi aventada a hipótese de que a imunidade mediada por células pode desempenhar papel importante no contrôle das I.C.R., uma vez que a melhora clínica dos pacientes foi acompanhada de positivação de testes cutâneos anteriormente negativos, testes estes realizados quer com o agente infeccioso específico, quer com antígeno inespecífico de refôrço. The treatment of relapsing chronic infections (RCI) encounters many difficulties. In the present study, the use of the immuno adjuvant P40 either alone or in association with vaccinotherapy for the treatment of RCI turned out to be very effective, whereas vaccinotherapy alone was not. It is hypothesized that cell-mediated immunity may play a major role in controlling RCI, since the clinical improvement of the patients kept up with the positivation of previously negative skin tests carried out with either the specific infecting agent or with recall-anti gens.