Synthesis and immunogenicity of PG-tb1 monovalent glycoconjugate.

A PG-tb1 hapten from the West Beijing strains of Mycobacterium tuberculosis cell wall has been efficiently synthesized and conjugated to CRM197 in a simple way as linker-equipped carbohydrate by applying squaric acid chemistry for an original neoglycoprotein, creating a potent T-dependent conjugate vaccine. The intermediate monoester can be easily purified and the degree of incorporation can be monitored by MALDI-TOF mass spectrometry. After administered systemically in mice without any adjuvant, the conjugate induced high antigen-specific IgG levels in serum. Furthermore, following the third immunization, significant antibody titers frequently exceeding 0.8 million were observed in the sera of mice vaccinated with PG-CRM197 conjugate which showed the potential for preparation of TB vaccine.

Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated acute phase atopic dermatitis by inducing regulatory T cells.

Increase in the number of patients with atopic dermatitis (AD) has been recently reported. T helper (Th) cells that infiltrate AD skin lesions are Th2-type dominant; reduced exposure to environmental Th1-cytokine-inducing microbes is believed to contribute to the increased number of AD patients. Regulatory type immune responses have been also associated with the occurrence of AD. It has been reported that antigen 85B (Ag85B) purified from mycobacteria is a potent inducer of Th1-type immune response in mice as well as in humans. In this study, we have examined the effect of plasmid DNA encoding Ag85B derived from Mycobacterium kansasii on AD skin lesions induced by oxazolone (OX) application. Th2-cytokine mediated mouse AD model with immediate type response followed by a late phase reaction was developed by repeated applications of low-dose OX to sensitized mice. Mice were immunized with plasmid DNA encoding cDNA of Ag85B before OX sensitization or during repeated elicitation phase. Both therapies were associated with significant suppression of immediate type response, clinical appearance, dermal cell infiltration, reduced IL-4 production, and augmented IFN-gamma mRNA expression compared to placebo-treated mice. Additionally, increased number of Foxp3(+) regulatory T cells were observed in the skin sections in Ag85B treated mice. The results of this study suggest that Ag85B DNA vaccine is a potential therapy for Th2 type dermatitis.

Una vacuna para la lepra: evaluación de su necesidad y estrategia de desarrollo

Las vacunas vivas atenuadas como la BCG aunque han demostrado capacidad de estimular una respuesta inmunológica protectora en humanos en algunos ensayos clínicos, no resultan actualmente las más apropiadas con la gran cantidad de infectados HIV ya que podrían por sí mismas ser causa de enfermedad. Este trabajo revisa las necesidades actuales y posibilidades de aplicación de una vacuna frente a la lepra diseñada con los planteamientos y conocimientos proporcionados por las nuevas tecnologías, sobre todo en los campos de la Inmunología y Biología Molecular (AU)

The 65 kDa protein of Mycobacterium habana and its putative role in immunity against experimental tuberculosis.

Mycobacteria including Mycobacterium tuberculosis and Mycobacterium leprae possess multiple antigens some of which inhibit other anti-mycobacterial immune responses. Whole cell vaccines are not free from these suppressive molecules and may adversely affect the immunogenic response(s). Purified protein components having only immunogenic properties should prove to be superior vaccine(s). Mycobacterium habana, a candidate vaccine for mycobacterial infections has been dissected for analysing its antigenic myriad. A 65 kDa protein of this mycobacterium has been isolated and characterized for its protective and cell mediated immune responses. The protein was isolated in pure form using an isotachophoresis (SDS-PAGE filtration) technique and identified with low molecular weight markers along with mAb using the immunoblot technique. Mab IIH9 has identified a 65 kDa protein in M. habana. This protein has been found to be immunoprotective in mice against M. tuberculosis H37Rv infection. It generates high levels of DTH responses in mice against M. tuberculosis and M. leprae antigens and inhibits migration of sensitized cells under the antigenic influence of homologous and heterologous origin. Possibilities of developing this protein as a subunit vaccine are discussed in this report.

[Immunomodulator treatment of multibacillary leprosy using extracts of microbial ribosomes]. / Traitement immunomodulant de la lèpre multibacillaire par extraits de ribosomes microbiens.

Ribomunyl can in practice be profitably included in the range of immunostimulants, but it requires weekly injections and hence surveillance that will also enable any adverse reactions to be monitored. Its action and tolerance after polychemotherapy have still to be studied. On the basis of our experience, we feel that only isoprinosine, whose effectiveness and good tolerance we have demonstrated, can be used for self-treatment in a mass campaign.