The first sign of trouble is often a sudden drop in newborn lambs. Then come the miscarriages, as dozens of goats, once healthy, lose their pregnancies in waves. Within weeks, an entire herd can be crippled by what farmers call an "abortion storm," a telltale marker of Q fever. Not long after, the human toll begins. Sheep shearers and farm workers start calling in sick, suffering from high fevers. This mystery fever, known as Q-fever, is caused by the bacterium Coxiella burnetii, which has significant impacts on agriculture and public health. Unlike dramatic outbreaks that make headlines, Q fever operates quietly. It’s hard to detect, but it can devastate farms over the course of months. It causes failed pregnancies, weakened animals, and farm workers falling ill with fevers that linger for months.
The economic toll is staggering. In Australia, where Q fever is endemic, outbreaks cost the agricultural sector millions each year in lost livestock, veterinary care, and human medical expenses. In the Netherlands, a Q fever outbreak from 2007 to 2010 was estimated to have caused over half a billion dollars in economic damages. The bacterium spreads easily: Infected animals and humans shed the pathogen. Even the dust kicked up by hooves can send billions of C. burnetii cells into the air, each one capable of infecting a new victim. Unlike seasonal illnesses that come and go, Q fever lingers in the soil, resurfacing with each new generation of livestock. Q fever’s resistance has led it to become a focus of biological weapons research.
Throughout the 1950s, human trials were conducted to determine the efficacy of Q fever as a bioweapon. Though rarely fatal, Q-fever is difficult to detect; its often-debilitating symptoms can last for years, including flu-like illness, chronic fatigue, endocarditis (a deadly heart inflammation), and hepatitis. It remains listed by the CDC as a Tier 2 bioterrorism agent, similar to toxins like ricin.
Dr. Gayathri Sam never expected to become an expert in livestock diseases. Trained in immunology in Sri Lanka, she first studied human infections, working in hospitals.
But when she moved to Australia for her PhD, she encountered the devastating reach of Q fever. As one of the countries with the highest rates of Q fever, Australia has implemented a series of programs to control the disease, including a Q fever registry to track infections and vaccinations, and vaccination programs targeting high-risk communities.
Dr. Sam’s research focuses on the immune system’s tangled response to C. burnetii, and its only existing vaccine, Q-VAX ®. The existing vaccine, Q-VAX®, is highly effective, but impractical for widespread use. Composed of inactivated C. burnetii whole cells, it can cause severe immune or allergic reactions, particularly in those already exposed to the disease. Several rounds of skin and blood tests are required to identify whether someone can take the vaccine, and the side effects are so severe that Q-VAX ® is not licensed for use anywhere else in the world. Now, under the mentorship of Prof. Bernd Rehm and Dr. Shuxiong Chen at the Rehm Group at the Centre for Cell Factories and Biopolymer within Griffith Institute for Biomedicine and Glycomics, Dr. Sam is working on two new vaccine candidates that aim to provide the same level of protection as Q-VAX ®, but without the risky side effects. Her research involves creating a solution that doesn’t just work in sterile laboratories, but in the field. The vaccine candidates she works with must be reaction-free, stable in varying temperatures, and effective in both human and animal models. This research builds on Prof. Bernd Rehm’s work, which focuses on developing self-organizing biological microstructures, such as the materials used to build Dr. Sam’s new vaccines.
Q fever’s tenacity stems from its two forms: a large-cell variant (LCV) and a small-cell variant (SCV). The SCV’s thick cell wall helps it endure heat, drying, and disinfectants, lingering in dust or soil for over a year. Inhaling even one SCV particle can cause illness. Inside the body, SCVs shift to LCVs, hiding inside immune cells and evading detection. These LCVs can revert to SCVs, creating reservoirs of dormant bacteria capable of reawakening and causing chronic Q fever. The two forms mean that a Q-fever aerosol could cause “mystery flu” outbreaks for years, followed by surges in rates of endocarditis and debilitating fatigue. Dr. Sam’s innovative vaccine candidates against Q fever serve not only to mitigate Q fever as an agricultural disease but also to strengthen national security against biological warfare.
To counter this pathogen, Dr. Sam, working under the supervision of Professor Bernd Rehm, is developing vaccines that train the immune system to recognize and eliminate the bacterium while avoiding harmful side effects. When a foreign invader enters the body, specialized cells called antigen-presenting cells (APCs) act as scouts, capturing pieces of the intruder and displaying them to other immune cells, priming them to search for and attack similar invaders. Traditional vaccines like Q-VAX® prime the body against the entire bacterium, potentially causing it to overreact to harmless bacteria. Dr. Sam’s work involves finding and training the body’s cells against the most specific markers of Q-fever, an immunological equivalent of training the security guards to identify a suspect by a unique tattoo rather than broad traits like height or gender.
The Two Vaccine Candidates Explained:
The T-Cell Trainer (CP-COX)
Dr. Sam’s first vaccine candidate involves training immune T-cells to recognize epitopes from C. burnetii. Epitopes are the most recognizable parts of foreign objects in the body, like distinctive facial features on a wanted poster. These are the specific parts that immune cells actually bind to and remember. To make sure the cells are trained specifically to recognize Q fever, the CP-COX vaccine doesn’t use whole cells. Rather, the vaccine is built on a platform developed by Professor Bernd Rehm and Dr. Shuxiong Chen called Cross-Reactive Material 197 (CRM197). CRM197 is a modified diphtheria toxin with its toxic properties removed but retaining its immune-stimulating ability. Chemically stitched onto CRM197 are eighteen epitopes from C. burnetii chosen through computer modeling and laboratory testing. The epitopes were selected for their ability to be recognized by immune cells, to stimulate diverse immune responses, and to represent different regions of the bacterium. CRM197 attracts the attention of the immune cells, which learn to recognize and attack the eighteen epitopes, or “faces” of Q fever. In addition to the immune system benefits, the modified vaccine components can be produced from genetically modified E. coli bacteria, allowing for low-cost, large-scale production.
The Protein Pair (CP-Com1/CP-YbgF)
Dr. Sam’s second vaccine candidate takes a more comprehensive approach by combining two complete bacterial proteins, Com1 and YbgF, with CRM197. These proteins produce complementary immune responses, each stimulating a different type of immune cell. The immune system learns to recognize multiple epitopes on the same protein, including ones not easily predicted through molecular models. When tested in guinea pigs, this vaccine produced antibody levels 1000x higher than Q-VAX®, and prevented fever responses even after exposure to the live pathogen.
Promising results in animals are only the beginning. Dr. Sam is now focused on refining the vaccine by carefully balancing a strong immune response with minimal side effects. This includes adjusting formulations to reduce inflammation, fine-tuning adjuvants (the immune-boosting components), and optimizing how antigens are presented. These refinements form the foundation for the first human trials. Alongside these efforts, Dr. Sam is also working on optimizing dosing strategies to further improve vaccine effectiveness.
Behind every successful vaccine is a network of collaborators, and for Dr. Sam’s research, one of these partners is Biomatik, a biotechnology company specializing in recombinant protein production. Biomatik helped optimize and produce recombinant YbgF and Com1 proteins for use in developing the second vaccine candidate. Biomatik and other companies offering gene synthesis and peptide synthesis services help accelerate academic breakthroughs by allowing researchers to outsource the more technically challenging aspects of research design.
For Dr. Sam, the immediate goals are clear as she works to advance Q fever vaccine candidates toward widespread use and distribution. In the future, the Rehm group seeks to continue using Cross-Reactive Materials to develop vaccines for other common diseases. Dr. Sam is proud of the progress she’s made so far, but she emphasizes that it’s a collaborative effort, saying, “ it would not have been possible to achieve this milestone without the support of my supervisor Prof. Bernd Rehm, co-supervisor Dr. Shuxiong Chen, and the rest of my lab mates who have helped me along the way.”