Development Of New Tuberculosis Vaccines Research Articles

Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues

In May 2005, the TB Vaccine Initiative of the World Health Organization (WHO) Initiative for Vaccine Research convened a working meeting of regulators, investigators, and clinicians from developing and developed countries involved in tuberculosis (TB) vaccine regulation and research (see Text S1 for a list of participants). The purpose of the meeting was to specifically discuss the regulatory challenges for testing and introducing investigative TB vaccines into countries where the disease is endemic.

Tuberculosis vaccine development

If the end of the 20th century saw the flowering of genomics, the beginning of the 21st century is witnessing an equally rapid blossoming of proteomics. These twin technologies have had a dramatic influence on the study of tuberculosis (TB), and nowhere more so than in the development of new TB vaccines. Only a few years ago, it was generally accepted that clinical trials of new TB vaccines would not take place for at least a decade. However, the first trials are now scheduled to start within months. Much TB vaccine research has thus shifted from developing new vaccines, to selecting the best vaccines for human use from the increasing number of effective new candidates becoming available. This selection is being eased by the improved animal models that have been developed over the past few years and by our increasing understanding of immunity to TB.

Vaccination of cattle against Mycobacterium bovis

Protection of cattle against bovine tuberculosis by vaccination could be an important control strategy in countries where there is persistence of Mycobacterium bovis infection in wildlife and in developing countries where it is not economical to implement a ‘test and slaughter’ control programme. Early field trials with Bacille Calmette Guerin (BCG) M. bovis vaccine in cattle produced disappointing results, with induction of tuberculin skin-test reactivity following vaccination and low levels of protection. However, recent studies using a low dose of BCG vaccine in cattle have produced more encouraging results and field trials should now be carried out in developing countries to determine whether this low dose BCG vaccination strategy will reduce the spread of infection. The options for new candidate tuberculosis vaccines have increased markedly in the last decade with the advent of new attenuated strains of M. bovis, and sub-unit protein and recombinant DNA vaccines. Some of these new types of vaccines have recently been tested in cattle. New attenuated M. bovis vaccines induced greater protection than BCG vaccine in cattle which had been sensitized to environmental mycobacteria prior to vaccination. In contrast, it has proved difficult to stimulate appropriate immune responses in cattle necessary for protection with sub-unit protein and recombinant DNA vaccines and better immunological adjuvants are required for these types of vaccines. Progress in the development of new tuberculosis vaccines has been very rapid in the past decade and the prospects for vaccination to control and eradicate bovine tuberculosis are encouraging.