Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is... more Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is mentioned in India’s Vedas, the most sacred texts of Hinduism, and later by Hippocrates, Celse D’Aretée de Cappadoce (170 bc), and Avicene (Calmette 1923; Calmette et al. 1928). Recently, genetic studies of the tubercle bacillus have found its progenitor to come into existence possibly as early as 35,000 bc (Gutierrez et al. 2005). Tuberculosis became an epidemic problem once humans settled and crowded into permanent, food-producing social networks. Thus, Egyptian mummies from the Rhamses period (3,000 bc) showed spinal deformities consistent with tuberculosis – Pott’s disease. Hippocrates used the term “phthisis,” the Greek term for “consumption,” to describe the wasting away experienced by individuals with tuberculosis. Swollen cervical lymph nodes were known as “scrofula” or the “King’s Evil” in England (Artenstein et al. 1995). The belief that they could be healed by the King’s touch, although coincidentally true in some cases, likely had more to do with host immune responses than regal intervention.
Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficien... more Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficiency virus (HIV) or simian immunodeficiency (SIV) antigens could be good candidates for the development of vaccines against AIDS. To develop effective HIV/SIV vaccines, humoral and cellular immune responses directed against multiple antigens may be essential for the control of the infection. In this study we immunized BALB/c mice via different mucosal routes (oral, aerogenic, nasal, and rectal) with a mixture of three rBCG strains expressing, respectively, the entire SIVmac251 Nef protein, and large fragments of the Env and Gag proteins. All routes of immunization studied induced immunoglobulin A (IgA) antibodies against mycobacterial PPD, SIV Env, and SIV Gag antigens in feces and bronchial lavages as well as specific immunoglobulin G (IgG) in serum. Strong, specific cytotoxic responses of splenocytes against Nef, Env, and Gag was observed whatever the mucosal route of immunization. Therefore, mucosal vaccination with a cocktail of rBCG strains induces local, specific IgA, systemic IgG, and systemic CTLs against the three SIV antigens expressed. Rectal and oral routes seemed the most appropriate route of vaccination to be used to protect against SIV infection.
BCG rectal administration to newborn and adult mice induced protective immune responses against t... more BCG rectal administration to newborn and adult mice induced protective immune responses against tuberculosis. BCG reaches the sub-epithelial site and the draining mesenteric lymph nodes (MLNs), and dendritic cells (DC) could be recruited to these sites. Using polarized Caco-2 epithelial cells, we showed that BCG translocates epithelial cells to basolateral compartment. Delayed in newborn BALB/c mice, an important recruitment of CD11c+ DCs, was documented in the rectal lamina propria and the MLNs during the first two weeks after rectal BCG delivery. In MLNs, two major DC subtypes were observed: conventional DCs (cDCs) (B220-) and plasmacytoid DCs (pDCs) (B220+). CIRE, mouse DC-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is predominantly expressed on pDCs and at a higher level on pDCs from the adult compared to newborn MLNs. cDCs with a higher capacity to induce the proliferation of naïve CD4+ T cells than pDCs, triggered CD4+ T cells to produce interferon-gamma whereas pDCs triggered them to release interleukin-10. Both DC subtypes equilibrates T cells as a source of microbicidal/microbiostatic signals and those acting as source of counter-inflammatory signals, preventing tissue damage and/or accelerating tissue repair. Thus, rectal delivery of BCG could be a safe and efficient route of vaccination against tuberculosis.
Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is... more Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is mentioned in India’s Vedas, the most sacred texts of Hinduism, and later by Hippocrates, Celse D’Aretée de Cappadoce (170 bc), and Avicene (Calmette 1923; Calmette et al. 1928). Recently, genetic studies of the tubercle bacillus have found its progenitor to come into existence possibly as early as 35,000 bc (Gutierrez et al. 2005). Tuberculosis became an epidemic problem once humans settled and crowded into permanent, food-producing social networks. Thus, Egyptian mummies from the Rhamses period (3,000 bc) showed spinal deformities consistent with tuberculosis – Pott’s disease. Hippocrates used the term “phthisis,” the Greek term for “consumption,” to describe the wasting away experienced by individuals with tuberculosis. Swollen cervical lymph nodes were known as “scrofula” or the “King’s Evil” in England (Artenstein et al. 1995). The belief that they could be healed by the King’s touch, although coincidentally true in some cases, likely had more to do with host immune responses than regal intervention.
Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficien... more Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficiency virus (HIV) or simian immunodeficiency (SIV) antigens could be good candidates for the development of vaccines against AIDS. To develop effective HIV/SIV vaccines, humoral and cellular immune responses directed against multiple antigens may be essential for the control of the infection. In this study we immunized BALB/c mice via different mucosal routes (oral, aerogenic, nasal, and rectal) with a mixture of three rBCG strains expressing, respectively, the entire SIVmac251 Nef protein, and large fragments of the Env and Gag proteins. All routes of immunization studied induced immunoglobulin A (IgA) antibodies against mycobacterial PPD, SIV Env, and SIV Gag antigens in feces and bronchial lavages as well as specific immunoglobulin G (IgG) in serum. Strong, specific cytotoxic responses of splenocytes against Nef, Env, and Gag was observed whatever the mucosal route of immunization. Therefore, mucosal vaccination with a cocktail of rBCG strains induces local, specific IgA, systemic IgG, and systemic CTLs against the three SIV antigens expressed. Rectal and oral routes seemed the most appropriate route of vaccination to be used to protect against SIV infection.
BCG rectal administration to newborn and adult mice induced protective immune responses against t... more BCG rectal administration to newborn and adult mice induced protective immune responses against tuberculosis. BCG reaches the sub-epithelial site and the draining mesenteric lymph nodes (MLNs), and dendritic cells (DC) could be recruited to these sites. Using polarized Caco-2 epithelial cells, we showed that BCG translocates epithelial cells to basolateral compartment. Delayed in newborn BALB/c mice, an important recruitment of CD11c+ DCs, was documented in the rectal lamina propria and the MLNs during the first two weeks after rectal BCG delivery. In MLNs, two major DC subtypes were observed: conventional DCs (cDCs) (B220-) and plasmacytoid DCs (pDCs) (B220+). CIRE, mouse DC-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is predominantly expressed on pDCs and at a higher level on pDCs from the adult compared to newborn MLNs. cDCs with a higher capacity to induce the proliferation of naïve CD4+ T cells than pDCs, triggered CD4+ T cells to produce interferon-gamma whereas pDCs triggered them to release interleukin-10. Both DC subtypes equilibrates T cells as a source of microbicidal/microbiostatic signals and those acting as source of counter-inflammatory signals, preventing tissue damage and/or accelerating tissue repair. Thus, rectal delivery of BCG could be a safe and efficient route of vaccination against tuberculosis.
Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is... more Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is mentioned in India’s Vedas, the most sacred texts of Hinduism, and later by Hippocrates, Celse D’Aretée de Cappadoce (170 bc), and Avicene (Calmette 1923; Calmette et al. 1928). Recently, genetic studies of the tubercle bacillus have found its progenitor to come into existence possibly as early as 35,000 bc (Gutierrez et al. 2005). Tuberculosis became an epidemic problem once humans settled and crowded into permanent, food-producing social networks. Thus, Egyptian mummies from the Rhamses period (3,000 bc) showed spinal deformities consistent with tuberculosis – Pott’s disease. Hippocrates used the term “phthisis,” the Greek term for “consumption,” to describe the wasting away experienced by individuals with tuberculosis. Swollen cervical lymph nodes were known as “scrofula” or the “King’s Evil” in England (Artenstein et al. 1995). The belief that they could be healed by the King’s touch, although coincidentally true in some cases, likely had more to do with host immune responses than regal intervention.
Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficien... more Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficiency virus (HIV) or simian immunodeficiency (SIV) antigens could be good candidates for the development of vaccines against AIDS. To develop effective HIV/SIV vaccines, humoral and cellular immune responses directed against multiple antigens may be essential for the control of the infection. In this study we immunized BALB/c mice via different mucosal routes (oral, aerogenic, nasal, and rectal) with a mixture of three rBCG strains expressing, respectively, the entire SIVmac251 Nef protein, and large fragments of the Env and Gag proteins. All routes of immunization studied induced immunoglobulin A (IgA) antibodies against mycobacterial PPD, SIV Env, and SIV Gag antigens in feces and bronchial lavages as well as specific immunoglobulin G (IgG) in serum. Strong, specific cytotoxic responses of splenocytes against Nef, Env, and Gag was observed whatever the mucosal route of immunization. Therefore, mucosal vaccination with a cocktail of rBCG strains induces local, specific IgA, systemic IgG, and systemic CTLs against the three SIV antigens expressed. Rectal and oral routes seemed the most appropriate route of vaccination to be used to protect against SIV infection.
BCG rectal administration to newborn and adult mice induced protective immune responses against t... more BCG rectal administration to newborn and adult mice induced protective immune responses against tuberculosis. BCG reaches the sub-epithelial site and the draining mesenteric lymph nodes (MLNs), and dendritic cells (DC) could be recruited to these sites. Using polarized Caco-2 epithelial cells, we showed that BCG translocates epithelial cells to basolateral compartment. Delayed in newborn BALB/c mice, an important recruitment of CD11c+ DCs, was documented in the rectal lamina propria and the MLNs during the first two weeks after rectal BCG delivery. In MLNs, two major DC subtypes were observed: conventional DCs (cDCs) (B220-) and plasmacytoid DCs (pDCs) (B220+). CIRE, mouse DC-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is predominantly expressed on pDCs and at a higher level on pDCs from the adult compared to newborn MLNs. cDCs with a higher capacity to induce the proliferation of naïve CD4+ T cells than pDCs, triggered CD4+ T cells to produce interferon-gamma whereas pDCs triggered them to release interleukin-10. Both DC subtypes equilibrates T cells as a source of microbicidal/microbiostatic signals and those acting as source of counter-inflammatory signals, preventing tissue damage and/or accelerating tissue repair. Thus, rectal delivery of BCG could be a safe and efficient route of vaccination against tuberculosis.
Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is... more Tuberculosis occurred in humans probably as early as 8,000 bc in its sporadic form. Indeed, it is mentioned in India’s Vedas, the most sacred texts of Hinduism, and later by Hippocrates, Celse D’Aretée de Cappadoce (170 bc), and Avicene (Calmette 1923; Calmette et al. 1928). Recently, genetic studies of the tubercle bacillus have found its progenitor to come into existence possibly as early as 35,000 bc (Gutierrez et al. 2005). Tuberculosis became an epidemic problem once humans settled and crowded into permanent, food-producing social networks. Thus, Egyptian mummies from the Rhamses period (3,000 bc) showed spinal deformities consistent with tuberculosis – Pott’s disease. Hippocrates used the term “phthisis,” the Greek term for “consumption,” to describe the wasting away experienced by individuals with tuberculosis. Swollen cervical lymph nodes were known as “scrofula” or the “King’s Evil” in England (Artenstein et al. 1995). The belief that they could be healed by the King’s touch, although coincidentally true in some cases, likely had more to do with host immune responses than regal intervention.
Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficien... more Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficiency virus (HIV) or simian immunodeficiency (SIV) antigens could be good candidates for the development of vaccines against AIDS. To develop effective HIV/SIV vaccines, humoral and cellular immune responses directed against multiple antigens may be essential for the control of the infection. In this study we immunized BALB/c mice via different mucosal routes (oral, aerogenic, nasal, and rectal) with a mixture of three rBCG strains expressing, respectively, the entire SIVmac251 Nef protein, and large fragments of the Env and Gag proteins. All routes of immunization studied induced immunoglobulin A (IgA) antibodies against mycobacterial PPD, SIV Env, and SIV Gag antigens in feces and bronchial lavages as well as specific immunoglobulin G (IgG) in serum. Strong, specific cytotoxic responses of splenocytes against Nef, Env, and Gag was observed whatever the mucosal route of immunization. Therefore, mucosal vaccination with a cocktail of rBCG strains induces local, specific IgA, systemic IgG, and systemic CTLs against the three SIV antigens expressed. Rectal and oral routes seemed the most appropriate route of vaccination to be used to protect against SIV infection.
BCG rectal administration to newborn and adult mice induced protective immune responses against t... more BCG rectal administration to newborn and adult mice induced protective immune responses against tuberculosis. BCG reaches the sub-epithelial site and the draining mesenteric lymph nodes (MLNs), and dendritic cells (DC) could be recruited to these sites. Using polarized Caco-2 epithelial cells, we showed that BCG translocates epithelial cells to basolateral compartment. Delayed in newborn BALB/c mice, an important recruitment of CD11c+ DCs, was documented in the rectal lamina propria and the MLNs during the first two weeks after rectal BCG delivery. In MLNs, two major DC subtypes were observed: conventional DCs (cDCs) (B220-) and plasmacytoid DCs (pDCs) (B220+). CIRE, mouse DC-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is predominantly expressed on pDCs and at a higher level on pDCs from the adult compared to newborn MLNs. cDCs with a higher capacity to induce the proliferation of naïve CD4+ T cells than pDCs, triggered CD4+ T cells to produce interferon-gamma whereas pDCs triggered them to release interleukin-10. Both DC subtypes equilibrates T cells as a source of microbicidal/microbiostatic signals and those acting as source of counter-inflammatory signals, preventing tissue damage and/or accelerating tissue repair. Thus, rectal delivery of BCG could be a safe and efficient route of vaccination against tuberculosis.
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Papers by Anne-Marie Balazuc