Scripps Institute researchers have developed an innovative dual action anthrax vaccine-antitoxin combination that could provide rapid treatment and long-term protection in only a single injection.
Tests on rats showed that their immune system against lethal toxins became stronger and improved faster with only one injection of the vaccine.
Concerns about anthrax-a potentially fatal disease caused by the spore-forming, gram-positive bacterium Bacillus anthracis-as a weapon of bioterrorism has prompted increased efforts to develop better antitoxins and vaccines.
Current anthrax treatment involves antibiotics such as ciprofloxacin and doxycycline that attack the bacteria but provide no protection against the dangerous toxins secreted by the bacteria.
The new study, on the other hand, introduces a highly effective dual-action compound that leapfrogs current efforts to develop a second-generation anthrax vaccine.
In the research, the scientists created a "multivalent display," with several sites of attachment for recombinant protective (PA), the primary component of the current anthrax vaccine, rather than only one.
Virus-like particles coated with PA were found to produce a potent toxin-neutralizing antibody response that protected rats from the lethal anthrax toxin after only a single immunization.
Scripps Research scientist Anette Schneemann, who developed the vaccine along with Marianne Manchester, and Salk Institute Prof. John A.T. Young, said the antitoxin strategy arose from the discovery of the anthrax toxin receptor, ANTXR2, in Prof. Young's lab.
"The new anti-anthrax agent is based on a multivalent display of ANTXR2 on the surface of an insect virus. Our approach was based on the assumption that a multivalent display of recombinant protective antigen protein would induce a far more potent immune response. That turned out to be correct," said Schneemann.
She said the new vaccine-antitoxin combination was based on the multivalent display (180 copies) of the PA-binding von Willebrand A (VWA) domain of the ANTXR2 cellular receptor on the Flock House virus.
The chimeric virus-like particle platform, which produces protective immunity and has been shown to be safe, inhibited lethal toxin action in vitro and in vivo models of anthrax infection, she said.
She said rats survived exposure to the toxin four weeks after a single injection of the new double-acting agent.
"This result suggests an extremely rapid production of neutralizing antibodies without the use of an adjuvant, a secondary agent that helps stimulate the immune system and is often used to increase the vaccine response-key goals for the development of third-generation anthrax vaccines," she said.
"The new anti-anthrax agent that we developed is an important and potentially critical development for anyone who works with the bacterium or those who might be exposed to it in a bioterrorism attack. While other strategies are being pursued to develop improved anthrax vaccines, none of these offer the distinct advantage of combining the function of a vaccine with a potent antitoxin," Schneemann added.
The study appears in the October 5 issue of the journal PLoS Pathogens.