When bacterial pathogens attack the surface of a cell, vaccine-induced antibodies can mount a formidable defense and fend off the bad bugs. The trouble comes when antibodies cannot recognize the pathogen because the bacteria have infected the cell and are hidden, growing inside the cell's wall.
To mount a defense against these cloaked attackers, Darren Higgins, Associate Professor of Microbiology at Harvard Medical School, and H.G. Archie Bouwer, Immunology Research Scientist at the Earle A. Chiles Research Institute and Portland VA Medical Center, have developed a vaccine strategy for generating an attenuated strain of an intracellular bacterial pathogen. The study appears in the PNAS online early edition the week of March 20, 2006. The vaccine approach could also protect against other intracellular bacterial pathogens, such as tularemia.
The team has initially applied their strategy to Listeria monocytogenes, which affects the most vulnerable humans - the chronically ill, the elderly, pregnant women, and young children, who are susceptible to a serious infection caused by eating food contaminated with the bacteria. In the United States, an estimated 2,500 persons become seriously ill with the infection each year. Of these, 500 die.
After absorption by antigen presenting cells, the attenuated Listeria strain does not replicate, and is readily killed. Unlike other attenuated Listeria strains that do not replicate in host cells, vaccine studies in animals showed that the new strain provided protection from challenge with a virulent, disease-causing, Listeria strain.
"For the first time, an attenuated strain of Listeria that does not replicate in an animal and does not require any manipulation of the bacterium or host prior to immunization still provides protective immunity," Higgins said.