Developing a vaccine against infections in patients with cystic fibrosis (CF) is challenging, and to succeed researchers need a deeper understanding of the natural history of CF lung infections. Joanna Goldberg, PhD, with Emory University School of Medicine, detailed the difficulties specific to such vaccine discovery in her talk, “Vaccines for CF Infections: Episode IV – A New Hope.”
The presentation was part of a symposium, “Challenges in CF Microbiology: Light Amid the Fog,” at the recent 30th Annual North American Cystic Fibrosis Conference (NACFC), held in Orlando, Florida.
Infections in CF can be caused by several microbes, most often bacteria. But studies show that what once was the natural history of these infections has changed. Early antibiotic treatment of Pseudomonas aeruginosa has now made Staphylococcus aureus the most commonly isolated bacteria in CF patients.
Infections with mucoid P. aeruginosa, however, remain the major initiator and driver of lung function decline in CF, and vaccination against this microbe is still a research priority.
When developing vaccines, researchers aim to identify epitopes — parts of surface proteins on bacteria — that if targeted are most likely to give results. But this approach is problematic, since bacteria tend to evolve rapidly to evade immune responses, changing their epitopes along the way.
The search for such structures becomes even more complicated, because individual bacteria of the same strain can carry different types of protein markers on their surface.
Researchers have also experimented with so-called live attenuated vaccines. Such vaccines are composed of versions of a microbe engineered to induce an immune response but not able to cause disease. This may not be the best approach for CF patients, however; scientists are concerned that an active vaccine that triggers T-cell immune responses can increase lung inflammation in patients.
New techniques to assess the composition of bacterial species also reveal that the bacterial communities in CF airways are quite complex. As of now, researchers do not know how some of the newly identified species contribute to disease, or how the removal of one species would affect the composition of the remaining microbes.
Current animal models poorly mirror the disease in humans, a common research complaint, but new models are being developed, Goldberg said.
Vaccines, naturally, need to be tested in patients, and to focus on specific patient groups. A difficulty is that such trials would need to identify patients not yet infected with the microbe in question.
In addition to classical vaccine strategies, researchers have considered treating patients with antibodies, an approach often called passive vaccination. Unlike traditional vaccines, antibodies can also be used during an infection.