Vaccines Could Prevent Common CVB Infections in CF: Study
Coxsackie B vaccine is being developed by Provention Bio with Vactech
Getting vaccinated against Coxsackie B viruses (CVB) may help prevent people with cystic fibrosis (CF) from getting ill, according to a new study of CF mouse models.
“This study shows that CVB infections are common in the CF population and we provide preclinical evidence that CVB infections are preventable through vaccination. As respiratory virus infections are strongly linked to exacerbated pulmonary morbidity in CF and vaccines preventing such infections are advocated in CF, we propose that the role of CVB infections in pulmonary exacerbations should be further studied,” the researchers wrote.
The study, “Coxsackievirus B infections are common in Cystic Fibrosis and experimental evidence supports protection by vaccination,” was published in iScience.
Coxsackie B viruses, or CVBs, are a group of viruses that commonly cause infections with nonspecific symptoms like fever, headaches, sore throat, fatigue, and muscle pain. In rarer cases, they can cause serious diseases like heart or liver inflammation. There are six common types of CVB (dubbed CVB1-6).
CVB infections are common during childhood in the general population, but they can also occur in adults. A vaccine against CVBs is currently being developed by Provention Bio in collaboration with Vactech. In a Phase 1 trial (NCT04690426) in 32 healthy volunteers , it showed a positive safety profile and met secondary efficacy goals.
Testing for Coxsackie B viruses
Scientists in Sweden and Finland tested for CVB in 65 people with CF, as well as 33 people without the disease, who served as controls. One of the study’s authors is the chairman of Vactech and serves (alongside another study author) on the scientific advisory board of Provention Bio.
“Whether CVB infections are common in CF has not been studied. However, if prevalent in this population, the CVB vaccine could be used prophylactically to prevent infections, thereby contributing to a lowering in the frequency of virus infections that cause upper respiratory tract symptoms,” the scientists wrote.
All the controls and 89% of the CF patients were seropositive for at least one CVB, meaning they had antibodies against the virus in their blood that suggested they’d had an infection in the past. On average, the CF patients were seropositive for 2.1 types of CVBs, while controls were positive for 2.8 types.
Additional comparisons based on age didn’t show substantial differences in CVB seropositive rates between the two groups.
“These results suggest that CVB infections are common in CF with a similar prevalence to healthy subjects,” the researchers wrote.
The scientists then examined the effects of a vaccine against CVB3 in CF mice harboring F508del, the most common CF-causing mutation found in roughly 90% of patients. The mice were given two injections of the vaccine, two weeks apart.
The vaccine was generally well tolerated by the CF animals. The only noted side effect being weight loss in two F508del mice, which was judged not likely related to the vaccine.
After receiving both doses, anti-CVB3 antibody levels were similar in the CF mice compared with mice without CF. Experiments using a different CVB3 vaccine — created based off of a different strain of the virus — yielded similar results and showed the vaccine was well tolerated and prompted antibody production that could neutralize the CVB3 virus.
“These data show that F508del mice are as capable as [wild-type] mice of raising virus nABs [neutralizing antibodies] after a booster vaccination,” the researchers wrote.
The researchers later vaccinated F508del mice with a three-dose vaccine regimen against either CVB1 or CVB3. Then they assessed how well the vaccinated mice were protected from infection by the respective viruses.
Whereas unvaccinated CF mice lost weight and had high levels of virus in the blood and peripheral organs within a few days of infection, vaccinated mice showed no signs of weight loss or systemic infection. Unvaccinated mice showed signs of damage in the pancreas, lungs, and liver, which were not found or were lower in vaccinated mice.
“Together, these results demonstrate that CVB vaccines protect F508del mice from acute CVB infections, viral dissemination to organs and virus-mediated tissue damage, including in the lung,” the researchers concluded, noting that, in the original group of CF patients, almost all had antibodies against the polio virus after having been vaccinated for it. Polio and CVBs are both part of a broad category of viruses called enteroviruses.
The researchers said the data show most people with CF should respond well to a CVB vaccine, but tests to confirm immunization-induced immunity should be performed routinely among them.