NEW YORK (Reuters Health) - A new study in mice suggests a good target for an intranasally administered vaccine against gonorrhea, researchers report in the July issue of Infection and Immunity.

There is currently no vaccine against Neisseria gonorrhoeae, notes Dr. Cynthia Nau Cornelissen of the Medical College of Virginia Campus of Virginia Commonwealth University in Richmond. Unlike its cousin N. meningitides, Dr. Nau points out, N. gonorrhoeae has no capsule, so efforts to develop a vaccine have focused on targeting the bacterium's surface proteins. These efforts have been hampered by the organism's ability to rapidly vary its surface structures.

Dr. Cornelissen and her team sought to determine whether the transferrin binding proteins (Tbp), which the bacterium uses to "hijack" its host's iron stores, would be a feasible target. Tbps are fairly consistent from strain to strain of N. gonorrhoeae, not subject to high frequency variation, and key to the bug's virulence. They tested an intranasal approach, which has been shown to be more effective than parenteral immunization in inducing antigen-specific IgA and IgG in the genital tracts of mice, primates and humans.

The researchers administered recombinant TbpA and TbpB to mice, together and separately, and conjugated to cholera toxin B (Ctb) subunit. Immune responses were measured in the animals' sera and genital tracts.

Response was stronger to TbpB when it was conjugated with Ctb, the researchers found, but the response to TbpA alone was as strong as when it was given along with Ctb.

While rTbpB was more immunogenic, producing higher levels of antigen-specific IgG and IgA, the researchers found, it was less likely to be protective across strains. However, the greatest bactericidal response was seen in serum of animals given both TbpA and TbpB conjugated with Ctb. RTbpA-specific sera had much stronger bactericidal activity than rTbpB, and also protected against both homologous and heterologous strains.

Another benefit to TbpA, Dr. Cornelissen told Reuters Health, is that it is more conserved from strain to strain than TbpB. "It might actually be the more stable target and easier to hit," she said. "We're hoping we can use that to our advantage, and essentially make this receptor its Achilles heel."

It's conceivable, Dr. Cornelissen points out, that a gonococcal vaccine targeting TbpA could be protective against N. meningitides as well, given that 80% of isolates have TbpA very similar to that of gonococcal organisms.

The next steps in the research, she added, will be to determine which parts of the Tbp proteins are needed to generate bactericidal antibodies, and testing whether antibodies to Tbp are protective against a model of infection.

Infect Immun 2005;73:3945-3953

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