Good Bacteria Can Be EZ Pass for Oral Vaccine Against Anthrax

The oral vaccine riding inside the good bacteria makes it way through the stomach and into the small intestine, an important immunological organ, where it easily and efficiently binds to cells that trigger an immune response – in this case, protection against anthrax in mice.

The finding, published the week of Feb. 16 in the online edition of Proceedings of the National Academy of Sciences, shows that an oral vaccine can be as effective as one given by needle, a potentially huge advance in drug delivery. Most vaccines are proteins, and as such normally won’t maintain their effectiveness after being digested in the stomach.

The good bacteria – Lactobacillus acidophilus, a lactic acid bacteria – are naturally found in dairy products like milk and cheese, and are added by manufacturers to foods like yogurt. They are used in food fermentationas, are safe for consumption and some are considered as probiotics that contribute to our general health and well being.

In the paper, Dr. Todd Klaenhammer, Distinguished University Professor and William Neal Reynolds Professor in the Department of Food, Bioprocessing and Nutrition Sciences, Dr. Tri Duong from the functional genomics program at NC State, and colleagues from the U.S. Army Medical Research Institute of Infectious Disease show that the acid tolerant lactic acid bacteria can act like an EZ Pass, delivering the anthrax vaccine through the stomach and releasing it into the small intestine.

There, the vaccine targets the first line of immune cells, dendritic cells, that can trigger the mucosal immune system to respond and elicit protection against anthrax. In the study, the oral vaccine worked about as well as a vaccine delivered by needle, the standard way of inoculating living things from viruses and pathogens.

“Normally, you can’t eat vaccines because the digestive process in the stomach destroys them, so vaccines are administered by needle,” Klaenhammer says. “But using ‘food grade’ lactic acid bacteria as a vehicle provides a safe way of getting the vaccine into the small intestine without losing any of the drug’s efficacy in binding to the dendritic cells, which can then trigger an immune response.”

Klaenhammer and his colleagues are now attempting to use lactic acid bacteria to carry varying types of oral vaccines to provide immunity to important viruses and pathogens. They are also working to improve the efficiency of binding of Lactobacillus acidophilus and the vaccine to dendritic cells.

“Can we make these generally recognized as safe lactic acid bacteria into a premier delivery system for vaccines and biotherapeutics? That’s the question we’re now trying to answer,” Klaenhammer says.

The study was funded by a grant from the National Institutes of Health and the North Carolina Dairy Foundation.

Note to editors: An abstract of the paper follows.

“Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge”
Authors: M. Mohamadzadeh, Northwestern University; T. Duong, Washington State University; S.J. Sandwick and T. Hoover, U.S. Army Medical Research Institute of Infectious Diseases; and Todd Klaenhammer, North Carolina State University;

Published: The week of Feb. 16, 2009, online in Proceedings of the National Academy of Sciences

Abstract: Efficient vaccines potentiate antibody avidity and increase T cell longevity, which confer protection against microbial lethal challenge. A vaccine strategy was established by using Lactobacillus acidophilus to deliver Bacillus anthracis protective antigen (PA) via specific dendritic cell-targeting peptides to dendritic cells (DCs), which reside in the periphery and mucosal surfaces, thus directing and regulating acquired immunity. The efficiency of oral delivery of L. acidophilus expressing a PA-DCpep fusion was evaluated in mice challenged with lethal B. anthracis Sterne. Vaccination with L. acidophilus expressing PA-DCpep induced robust protective immunity against B. anthracis Sterne compared with mice vaccinated with L. acidophilus expressing PA-control peptide or an empty vector. Additionally, serum anti-PA titers, neutralizing PA antibodies, and the levels of IgA-expressing cells were all comparable with the historical recombinant PA plus aluminum hydroxide vaccine administered s.c. Collectively, development of this strategy for oral delivery of DC-targeted antigens provides a safe and protective vaccine via a bacterial adjuvant that may potentiate mucosal immune responses against deadly pathogens.

Dr. Todd Klaenhammer, 919/515-2972 or klaenhammer@ncsu.edu