A team of researchers has now engineered a virus nanoparticle vaccine against Bacillus anthracis and Yersinia pestis, tier 1 agents that pose serious threats to national security of the United States. B. anthracis and Y. pestis are the pathogens that cause anthrax and plague, respectively. The study is published in mBio, an open-access journal of the American Society for Microbiology.

A team of researchers has now engineered a virus nanoparticle vaccine against  Bacillus anthracis  and  Yersinia pestis , tier 1 agents that pose serious threats to national security of the United States. B. anthracis and  Y. pestis are the pathogens that cause anthrax and plague, respectively. Using bacteriophage T4, the scientists developed the vaccine by incorporating key antigens of both  B. anthracis  and  Y. pestis  into one formulation.

Two doses of this vaccine provided complete protection against both inhalational anthrax and pneumonic plague in animal models. Even when animals were threatened with lethal doses of both anthrax lethal toxin and  Y. pestis CO92 bacteria, the vaccine was shown to be effective.

Causative agents

Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, are two of the deadliest pathogenic bacteria that have been used as biological warfare agents. Although Biothrax is a licensed vaccine against anthrax, no Food and Drug Administration-approved vaccine exists for the plague.

Here, we report the development of a dual anthrax-plague nanoparticle vaccine employing bacteriophage (phage) T4 as a platform. Using an in vitro assembly system, the 120- by 86-nm heads (capsids) of phage T4 were arrayed with anthrax an plague antigens fused to the small outer capsid protein Soc (9 kDa).

Antigens 

The antigens included the anthrax protective antigen (PA) (83 kDa) and the mutated (mut) capsular antigen F1 and the low-calcium-response V antigen of the type 3 secretion system from Y. pestis (F1mutV) (56 kDa). These viral nanoparticles elicited robust anthrax- and plague-specific immune responses and provided complete protection against inhalational anthrax and/or pneumonic plague in three animal challenge models, namely, mice, rats, and rabbits.

Protection was demonstrated even when the animals were simultaneously challenged with lethal doses of both anthrax lethal toxin and Y. pestis CO92 bacteria. Unlike the traditional subunit vaccines, the phage T4 vaccine uses a highly stable nanoparticle scaffold, provides multivalency, requires no adjuvant, and elicits broad T-helper 1 and 2 immune responses that are essential for complete clearance of bacteria during infection.

Therefore, phage T4 is a unique nanoparticle platform to formulate multivalent vaccines against high-risk pathogens for national preparedness against potential bioterror attacks and emerging infections.

"This dual anthrax-plague vaccine is a strong candidate for stockpiling against a potential bioterror attack involving either one or both of these biothreat agents," the researchers noted in the study. Their results demonstrate that T4 nanoparticle is a novel platform for developing multivalent vaccines against pathogens of high public health concern.