Evaluation of a ricin vaccine candidate (RVEc) for human toxicity using an in vitro vascular leak assay.

To protect against ricin intoxication, a genetically derived ricin A chain vaccine candidate (RVEc) was developed lacking the toxic N-glycosidase activity (Olson et al., 2004). The vaccine protects animals against an aerosolized ricin holotoxin (RT) challenge (Carra et al.

An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock.

Background: Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy.

Methods: As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures.

Improved formulation of a recombinant ricin A-chain vaccine increases its stability and effective antigenicity.

Ricin is a potent toxin associated with bioterrorism for which no vaccine or specific countermeasures are currently available. A stable, non-toxic and immunogenic recombinant ricin A-chain vaccine (RTA 1-33/44-198) has been developed by protein engineering. We identified optimal formulation conditions for this vaccine under which it remained stable and potent in storage for up to 18 months, and resisted multiple rounds of freeze-thawing without stabilizing co-solvents.

Recombinant C fragment of botulinum neurotoxin B serotype (rBoNTB (HC)) immune response and protection in the rhesus monkey.

Botulinum neurotoxin B (BoNTB) is a distinct protein subtype of a family of neurotoxins with the potential for use in biological warfare or terrorist attacks. This study is one in a series evaluating the immunogenicity and protective effects of recombinant vaccines against the different subtypes of botulinum toxin. The recombinant subunit vaccines encoding the C fragment portion ( approximately 50 kDa) of the toxins are produced in the yeast, Pichia pastoris.

Improved stability of a protein vaccine through elimination of a partially unfolded state.

Ricin is a potent toxin presenting a threat as a biological weapon. The holotoxin consists of two disulfide-linked polypeptides: an enzymatically active A chain (RTA) and a galactose/N-acetylgalactosamine-binding B chain. Efforts to develop an inactivated version of the A chain as a vaccine have been hampered by limitations of stability and solubility.

Comparative efficacy and immunogenicity of Q fever chloroform:methanol residue (CMR) and phase I cellular (Q-Vax) vaccines in cynomolgus monkeys challenged by aerosol.

Preliminary evidence gathered in rodents and livestock suggested that a phase I chloroform:methanol residue (CMR) extracted vaccine was safe and efficacious in protecting these animals from challenge with the obligate phagolysosomal pathogen (Coxiella burnetii). Prior to the initiation of phase II studies in human volunteers, we compared, in non-human primates (Macaca fascicularis), the efficacy of CMR vaccine with Q-Vax, a licensed cellular Australian Q fever vaccine that has been demonstrated to provide complete protection in human volunteers. Vaccine efficacy was assessed by evaluating thoracic radiographs and the presence of fever and bacteremia in monkeys challenged by aerosol with Coxiella burnetii.

Oral immunization of mice with ricin toxoid vaccine encapsulated in polymeric microspheres against aerosol challenge.

Mucosal (oral) immunization of mice with carrier-delivered ricin toxoid (RT) vaccine was accomplished by one long (7 weeks) or two short (4 weeks) immunization schedules. For the long and short immunization schedule two lots of vaccine were administered prepared with the same procedure but at different occasions. The long schedule consisted of a total of seven doses of 50 microg of vaccine in microencapsulated (lot #108) or aqueous form administered on days 1, 2, 3, 28, 29, 30 and 49.