Biomedical subjects

Melles Haile

Publications and source records attributed to Melles Haile.

3 recordsLinked to original sources

PubMed2005

Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis.

We hypothesized that the ability of BCG vaccination to protect against Mycobacterium tuberculosis is less in hosts exposed to chronic helminthes infection compared to unexposed individuals. To test this hypothesis we evaluated the efficacy of BCG vaccination in protecting against M. tuberculosis challenge in Schistosoma mansoni pre-infected mice by analyzing their ability to limit the replication of TB bacilli in the lung and liver and the histology of lung sections. The results show that BCG vaccinated mice with prior S. mansoni infection show significantly higher number of colony forming units of TB bacilli as well as significant reduction in air exchange area in the lung compared to controls. In addition, spleen cells from S. mansoni infected mice were found to produce significantly less IFN-gamma and nitric oxide when stimulated in vitro with PPD and several fold higher soluble egg antigen (SEA) and Concanavalin A induced IL-4 and IL-5 secretion. Taken together, our data show that S. mansoni infection reduces the protective efficacy of BCG vaccination against M. tuberculosis possibly by attenuation of protective immune responses to mycobacterial antigens and/or by polarizing the general immune responses to the Th2 profile.

Animals↗

PubMed2005

Recent developments in tuberculosis vaccines.

PURPOSE OF REVIEW: The aim is to review findings related to the use of Bacille Calmette-Guerin (BCG) vaccine, focusing on its limitations and benefits in controlling tuberculosis (TB). Some new TB vaccines, which have entered or are expected to enter clinical trials, are highlighted. RECENT FINDINGS: BCG is currently the only available vaccine against TB, and is widely administered within the World Health Organization Expanded Programme for Immunization. Several trials have shown that the protective efficacy of BCG varies between different populations. Recently, a 60-year follow-up study of American Indians reported the long-term efficacy of BCG to be 52%. The reasons for the low efficacy of the BCG vaccine may be generic differences in the BCG strains, differences in immunological properties of study populations or exposure to environmental factors such as mycobacteria. The low efficacy of the BCG vaccine has encouraged the search for a new vaccine. Among new vaccine candidates are live attenuated Mycobacterium tuberculosis vaccines, recombinant BCG, DNA vaccines, subunit vaccines and fusion proteins with novel adjuvants and delivery systems. SUMMARY: Today, most of the world's population is vaccinated with BCG. It is generally accepted that BCG protects against childhood TB but this immunity wanes with age, resulting in no or insufficient protection against TB. Using modern techniques, several research groups have developed more than 200 new vaccine candidates. Some of these vaccines are now in clinical trials. The clinical evaluation of these new vaccines should be designed to cover a heterogeneous population with great variation in immune responses.

Adult↗

PubMed2003

Mycobacterium tuberculosis arabinomannan-protein conjugates protect against tuberculosis.

Lipoarabinomannan (LAM) is a major structural surface component of mycobacteria. Arabinomannan (AM) oligosaccharides derived from LAM of Mycobacterium tuberculosis H37Rv were isolated and covalently conjugated to tetanus toxoid (TT) or to short-term culture filtrate proteins (antigen 85B (Ag85B) or a 75kDa protein) from M. tuberculosis strain Harlingen. The different AM oligosaccharide (AMOs)-protein conjugate vaccine candidates proved to be highly immunogenic, inducing boosterable IgG responses against the AMOs portion of the conjugates in rabbits and guinea-pigs. Proliferation of T-cells from C57BL/6 mice immunized with the conjugates was seen upon in vitro stimulation with PPD. In C57BL/6 mice subcutaneous immunization with the AMOs-antigen 85B conjugate in alum provided significant protection compared to sham (alum only) immunized mice (P < 0.021) as estimated by long term survival against intravenous challenge with 10(5) M. tuberculosis H37Rv. Subcutaneous immunization followed by nasal boost with an AMOs-TT conjugate in Eurocine L3 adjuvant provided high (P < 0.025) protection as determined by long term survival after intranasal challenge with 10(5) virulent M. tuberculosis strain Harlingen. This level of protection was comparable to that obtained with the conventional live attenuated BCG vaccine. In guinea-pigs, immunization with AMOs-Ag85B in Eurocine L3 adjuvant followed by aerogenic challenge with M. tuberculosis H37Rv resulted in increased survival and reduced pathology in lungs and spleens relative to non-immunized animals.

Adjuvants, Immunologic↗