Tuberculosis Vaccine

Research in the area of tuberculosis vaccines reported from Crucell Holland BV

Tuberculosis Vaccine Library Library Home This article was published in Biotech Business Week, which you can subscribe to online.

"Recombinant adenovirus (rAd) vectors are especially suited to the induction of strong T-cell immunity and thus represent promising vaccine vehicles for the prevention of TB. We have previously reported on rAd vector serotype 35, the serotype of choice due to low preexisting immunity worldwide, which expresses a unique fusion protein of Mycobacterium tuberculosis antigens Ag85A, Ag85B, and TB10.4 (Ad35-TBS). Here, we demonstrate that Ad35-TBS confers protection against M. tuberculosis when administered to mice through either an intranasal or an intramuscular route. Histological evaluation of lung tissue corroborated the protection and, in addition, demonstrated differences between two mouse strains, with diffuse inflammation in BALB/c mice and distinct granuloma formation in C57BL/6 mice. Epitope mapping analysis in these mouse strains showed that the major T-cell epitopes are conserved in the artificial fusion protein, while three novel CD8 peptides were discovered. Using a defined set of T-cell epitopes, we reveal differences between the two mouse strains in the type of protective immune response, demonstrating that different antigen-specific gamma interferon (IFN-gamma)-producing T cells can provide protection against M. tuberculosis challenge. While in BALB/c (H-2(d)) mice, a dominant CD8 T-cell response was detected, in C57BL/6 (H-2(b)) mice, more balanced CD4/CD8 T-cell responses were observed, with a more pronounced CD4 response in the lungs," wrote K. Radosevic and colleagues, Crucell Holland BV.

The researchers concluded: "These results unify conflicting reports on the relative importance of CD4 versus CD8 T-cell responses in protection and emphasize the key role of IFN-gamma."

Radosevic and colleagues published their study in Infection and Immunity (Protective immune responses to a recombinant adenovirus type 35 tuberculosis vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of gamma interferon. Infection and Immunity, 2007;75(8):4105-15).

For more information, contact K. Radosevic, Crucell Holland BV, Archimedesweg 4-6, 2333 CN Leiden, Netherlands.

Publisher contact information for the journal Infection and Immunity is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Netherlands, Adenoviridae, Biotechnology, Biotechnology Business, Biotechnology Company, Cellular, Crucell Holland BV, Gene Therapy, Immunization, Infectious Disease, Interferon, Mycobacteria, Mycobacterium Tuberculosis, Tuberculosis Vaccines, Vaccination, Viral, Virus.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.