Cue antigens for Q fever

Since the discovery of anthrax spores in letters in the US mail, a great amount of time, energy and money has been spent trying to identify potential biological warfare agents and search for suitable vaccine candidates. One such organism is Coxiella burnetii, the highly infectious agent of Q fever that is resistant to heat and drying and can be transported through the air and inhaled by humans. The US Centers for Disease Control and Prevention (CDC) declared that a single C. burnetii organism may cause disease in a susceptible person.

Although Q fever is rarely lethal in humans, with only 1-2% of those infected dying of the disease, it can bring on such severe conditions as pneumonia and hepatitis. It is very debilitating but most patients will recover within several months without any treatment. Q-fever is a notifiable disease in the US but not in many other countries so it is probably under-reported.

Under "normal" conditions outside of biological warfare, the principal way of contracting the disease is via inhalation, especially at farms where the organism affects livestock.

There are only two commercial diagnostic assays at present and they require purified organisms as antigens, which is a hazardous practice. So, scientists in the US have undertaken a study of the humoral immune response to try and identify seroactive antigens which might be useful for diagnosis and as components vaccines.

Adam Vigil from the University of California, Irvine, with colleagues from Antigen Discovery, Inc., Irvine, the Naval Medical Research Center, Silver Spring, MD, and the Uniformed Services University of the Health Sciences, Bethesda, MD, used a large protein array for their discovery experiments. A total of 1901 open-reading frames from C. burnetii, covering 84% of the entire proteome, were printed on a microarray.

The array was then probed with sera from 40 patients with Q fever and 20 healthy controls and the bound antibodies were detected by laser fluorescence after the application of a reagent that binds to them. A number of suitable candidates appear to have been found.

From 21 seroactive antigens, 13 were markedly more reactive in Q fever patients than in the controls but the remaining 8 were cross-reactive in disease and control sera, rendering them ineffective for this purpose.

A subset of the antigens that were active only for Q fever sera were used to produce an immunostrip for testing their viability in a form that could be used universally for diagnosis. This proof-of-concept experiment was used to test all of the serum samples and 9 of the antigens gave positive results, suggesting that they could be used in diagnostic tests.

Immunostrips provide an inexpensive alternative to the currently available tests and are simple to operate, but more work will be required to test the suitability of this arrangement for a Q fever test.

The same 9 seroactive antigens from the immunostrip also hold promise as vaccine candidates.

Apart from this set of 21 antigens, a further 64 displayed variable reactivity, emphasising the diversity of the humoral immune response to Q fever. Although they were rejected as diagnostic candidates due to this variability, the researchers declared that they could "provide novel insight into pathogenesis and the diversity of the immune response."

Overall, the results confirm that the immunoresponse to Q fever is very limited, with a very small number of seroactive antigens. Nonetheless, the microarray approach using ORF clones of almost the whole proteome has produced a number of candidates for vaccine components and for the diagnosis of Q fever.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.