Vaccine Patch Protects Against Lethal Anthrax Challenge

NEW YORK (Reuters Health) - Transcutaneous immunization (TCI) with a topical patch protects mice against challenge with lethal doses of aerosolized Bacillus anthracis, according to a report in the August 15th issue of The Journal of Infectious Diseases.

"Patch vaccination appears to be as safe and immunogenic as the traditional parenteral approaches," Dr. Richard T. Kenney from IOMAI, Gaithersburg, Maryland told Reuters Health. "We are in the middle of the first clinical trial, although we do not yet have results."

"The skin is a highly attractive immune environment that can be safely manipulated for the purposes of vaccination," he explained. "TCI allows delivery of all classes of vaccine components to the skin, from peptides to whole organisms, resulting in robust immune responses."

Dr. Kenney and colleagues vaccinated mice and rabbits with recombinant protective antigen (rPA) of B. anthracis and measured their responses. The investigators then tested its efficacy against a lethal aerosolized challenge in A/J mice, whose C5 deficiency renders them incapable of forming the membrane complex needed to kill bacteria.

The antibody response to TCI with rPA and E. coli heat-labile toxin as adjuvant was equivalent to that seen after intramuscular administration of rPA, the authors report, and a strong recall response was seen in all groups after only two vaccinations.

Animals that received TCI with the highest doses of rPA and heat-labile toxin had four times the number of rPA-specific IgG-secreting cells in lymph nodes compared with those seen after TCI with rPA alone. A higher response was also seen in the lungs of vaccinated animals.

All mice that had received rPA, whether by TCI or by injection, survived pulmonary challenge with B. anthracis 5 weeks after the last vaccination, the researchers note, compared with no survivors among naïve mice or mice that received heat-labile toxin alone.

The rPA and heat-labile toxin, formulated as a dry adhesive patch, induced strong IgG responses in mice and rabbits, the investigators report, confirming that a "formulated adhesive anthrax vaccine patch could deliver rPA to the epidermis to elicit robust and functional rPA responses.

"We currently have clinical programs in influenza, anthrax and a traveler's diarrhea vaccine and an expanding pipeline in various stages of preclinical development," Dr. Kenney added.

"We have now dosed over 1500 people in various studies with more than 2500 vaccinations, including several phase II double-blind, randomized, placebo-controlled trials, and have no indication that there are significant safety concerns."

Source: J Infect Dis 2004;190:774-780. [ Google search on this article ]

MeSH Headings: Animal Diseases : Disease Models, Animal : Diseases