Bacterial Membrane Proteins Generate Broad-Spectrum Immune Protection

A new generation of vaccines against bacterial pathogens may be based on affinity to common cross-genus or cross-species membrane proteins rather than to serotype specific polysaccharide antigens.

Investigators at the University of Pittsburgh School of Medicine (PA, USA) used the bacterium Klebsiella pneumoniae to establish a model respiratory disease in a population of laboratory mice. When the animals were exposed to heat-killed K. pneumoniae, they eventually developed an antibody response that protected them from subsequent challenge with living organisms of the same strain. However, these antibodies provided little protection from infection by different serotypes of the bacteria.

Results published in the December 23, 2011, issue of the journal Immunity, revealed that in addition to the antibody response, which was directed at capsular polysaccharides, the mice also increased production of T helper 17 cells (Th17) in response to conserved outer membrane proteins that conferred protection against several serotypes of K. pneumoniae.

Th17 cells are a subset of T helper cells producing interleukin 17 (IL-17) discovered in 2007. Initially, Th17 cells were broadly implicated in autoimmune disease, and auto-specific Th17 cells were shown to be highly pathologic. A more natural role for Th17 cells was suggested by studies that demonstrated preferential induction of IL-17 in cases of host infection with various bacterial and fungal species. Th17 cells primarily produce two main members of the IL-17 family, IL-17A and IL-17F, which are involved in the recruitment, activation, and migration of neutrophils. Th17 cells respond to protein complexes in the bacterial cell membrane. Those proteins, which are integral to the structure of the cell membrane, tend to be similar across bacterial strains, unlike the capsular polysaccharides, which are variable.

Senior author Dr. Jay K. Kolls, professor of pediatrics and immunology at the University of Pittsburgh School of Medicine, said, "Some current vaccines require generating a response to a number of these capsular sugars for effective immunization. An approach that harnesses the stability of the Th17 cell response to common proteins has the potential to simplify vaccination and provide a broader spectrum of coverage. This strategy may be particularly useful against bacteria that have diverse capsular sugars or multidrug resistant organisms."

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