CMVPepVax vaccine reduces complications post stem cell transplants

December 23, 2015 | by Jyoti Madhusoodanan

Between 50 and 80 percent of adults in the United States harbor a virus named CMV, or cytomegalovirus. CMV lies latent and harmless in most people. But in pregnant women or immunocompromised patients, the virus can flare up to cause infections and a form of hepatitis. 
 
Despite preemptive therapy, CMV infections are one of the most common complications in recipients of stem cell transplants. Further, the antiviral drugs used to prevent flare-ups are toxic, expensive, and increase the risk of other opportunistic infections. 
 
In the results of a phase 1b clinical trial published Dec. 23 in The Lancet Haematology, City of Hope researchers report that an anti-CMV vaccine, known as CMVPepVax, is safe and elicits a protective immune response when administered to stem cell transplant recipients.
 
“There was no hint that the vaccine is dangerous or causes side  effects. Second, we saw a reduction in CMV levels circulating in blood in most cases,” said City of Hope hematologist Ryotaro Nakamura, M.D., a first author on the study. 
 
The trial included 36 patients receiving stem cell transplants for lymphoma, leukemia or other diseases. Half the trial participants received doses of CMVPepVax, mixed with an adjuvant to boost immune response, at 28 days and at 56 days after the transplant.
 
Impressive results
 
At 100 days post-transplant, the researchers found that vaccinated patients had 2.5-fold more protective T cells against CMV, showed less CMV reactivation, and used fewer antiviral drugs. Nakamura presented the results of this trial at a symposium at the American Society of Hematology annual meeting in Orlando, Florida. 
 
“Overall, people who received the vaccine had more robust immune recovery than those in the observation group,” Nakamura said. “I was surprised because I didn’t expect to see such a dramatic difference between the two groups in such a small sample study.” 
 
The results of this early clinical trial have led to a larger, double-blind study now underway in collaboration with the University of Minnesota, Nakamura said. 
 
The CMVPepVax as currently designed only covers about 40 percent of the U.S. population. But with a few changes to one form of a small protein, it could be made in versions that would serve nearly 90 percent of individuals. Because the vaccine boosts immune response, it could minimize the use of – and toxic side effects of -- currently used anti-viral drugs against CMV. 
 
In addition to the immune response among patients receiving the vaccine, the researchers also observed a small, and surprising, difference between the two groups: Patients who received the vaccine experienced fewer relapses of leukemia (or other underlying disease), and also had a lower risk of mortality from nonrelapse related conditions. 
 
“We didn’t anticipate this to happen,” said Don J. Diamond, Ph.D., who chairs the Department of Experimental Therapeutics at Beckman Research Institute of City of Hope. “Yet we found this striking signal from the data, which told us that those in the vaccine arm of the trial were less likely to relapse of their disease and less likely to develop problems that would lead to nonrelapse mortality.” 
 
More study needed
 
Nakamura and Diamond caution that these beneficial results are not firm conclusions. These preliminary hints will need to be validated in a larger, blinded clinical trial that is currently underway, Diamond said. 
 
Precisely why or how vaccinating against CMV might exert protective effects is unknown. “If some of these benefits are substantiated in future studies, perhaps the vaccine might be of greater value to other populations,” Diamond said.
 
For now, the researchers are focused on bringing the vaccine into clinical use for patients receiving stem cell transplants. In the future, CMVPepVax may help expand the therapeutic repertoire for patients undergoing solid organ transplants or in other diseases. 
 
“The current National Cancer Institute-funded phase 2 trial will tell us whether the protective effects are really valid,” said Diamond. “If they are, it would be quite exciting.” 
 
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Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant numbers 5R01 CA-077544, 1R01-CA181045 and P30-CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
 

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