Michèle Mock's team, at the Institut Pasteur (Toxin and Bacterial Pathogenesis Unit - CNRS URA 2172), developed an experimental vaccine against anthrax disease. This work, about to be published in Infection and Immunity, shows the efficiency of an original and innovative vaccine combination. From these results observed on animals, researchers hope they develop a vaccine that could be used in humans.
Anthrax - affecting mammals, including humans as highlighted in the recent bioterrorist events - is caused by the bacteria Bacillus anthracis, which survives in the environment as a resistant form called spore. Once they enter the body, spores germinate to turn into bacilli (rod-shaped bacteria) that produce toxins, and multiply rapidly. Toxaemia and septicaemia, if not treated, lead to death.
No vaccine that is both side effect free and highly protective against virulent strains of the anthrax bacillus is available yet for humans. Today, there is an acellular vaccine, developed in the sixties in the U.S. and the UK: it is made up of one component of the two toxins from the bacterium, the PA protein (protective antigen). However, this vaccine requires several immunizations, and above all appears to be less efficient than the attenuated vaccine, made of live spores, that is successfully used on animals. However, the live vaccine, because of its toxic side effects, is considered inappropriate for use in humans.
The protection given by the existing acellular vaccine (the PA protein) is used to prevent toxin effect, but it does not affect the infection due to the multiplication of the bacilli. Researchers based their study on the fact that improving this vaccine should imply targeting the early stage of infection as well: to that end, spores must be neutralized as soon as they enter the body, thereby preventing the germination stage.
Thus, Michèle Mock's team tested a vaccine combination consisting of a purified PA (main constituant of the current acellular vaccine) to which were added killed spores (inactivated with formaldehyde).
This combination has been experimented on guinea pigs - animals that are frequently used to test vaccines against anthrax-, and on mice that are highly sensitive to the infection, and thus difficult to protect.
A complete protection from virulent strains of Bacillus anthracis was successful on both animal models, under conditions where immunization through the PA protein only, was unsuccessful.
Researchers believe this vaccine combination "may serve as the basis for the first design, for human use, of a subunit vaccine as protective as the current live veterinary vaccine".
The Institut Pasteur team now endeavours to
describe the different processes of the immune response induced by the experimental
vaccine, and to identify the spore components specifically involved in the
- "Anthrax spores make an essential contribution to vaccine efficacy": Infection and Immunity. February 2002, p.661-664.
Fabien Brossier, Martine Levy and Michèle MockToxin and Bacterial Pathogenesis Unit - CNRS URA 2172, Institut Pasteur, 75725 PARIS Cedex 15, France
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