September 13, 2019

Early effort to thwart chikungunya infection shows positive results

Phase 1 trial results in new approach to combat the chikungunya

Moderna Inc., a biotechnology firm in Cambridge, Massachusetts, this week announced positive results from a Phase 1 clinical study in healthy adults of a new approach to combat the chikungunya virus developed in partnership with scientists at Vanderbilt University Medical Center.

Chikungunya is an emergent, mosquito-borne tropical viral infection that can cause chronic and debilitating joint pain and arthritis. The study is testing whether injection of genetic material will trigger rapid production of a specific antibody in humans at levels that will neutralize the virus.

The anti-chikungunya antibody, called CHKV-24, was isolated in the lab of James Crowe Jr., MD, at VUMC from the blood of a previously infected person who had developed potent immunity against the virus.

With colleagues at Moderna, the researchers determined the antibody’s intermediate genetic blueprint, the messenger or mRNA, which in stepwise fashion is transcribed from the gene, the DNA, and then translated into the antibody protein.

Normally mRNA is rapidly degraded in the bloodstream. To protect it, the Moderna team encapsulated it in a lipid nanoparticle using in their proprietary technology. Pre-clinical studies suggested that once injected, cells will take up the encapsulated mRNA and begin producing antibody. That is what was observed in the current study.

“This study shows for the first time the ability to generate therapeutic levels of a complex protein in humans through systemic administration of an mRNA, essentially instructing the body to make its own medicines,” Tal Zaks, MD, PhD, chief medical officer at Moderna, said in a news release.

“Protection against infectious diseases like chikungunya is urgently needed around the world,” Crowe added. “These exciting data demonstrate a new way to address infectious diseases that uses mRNA to make antibodies in humans, establishing a powerful technology that could be deployable in a pandemic setting.”

Crowe is the Ann Scott Carell Professor in the Departments of Pediatrics and of Pathology, Microbiology & Immunology at Vanderbilt University School of Medicine and director of the Vanderbilt Vaccine Center.

At all dose levels and in all 22 participants in the study, administration of the genetic material, called mRNA-1944, triggered production of the CHKV-24 antibody at levels that are expected to be protective against chikungunya infection.

 In its news release Moderna outlined adverse effects including transient elevated heart rate observed in one of the participants given the highest dose of mRNA-1944. Company officials noted that no serious adverse effects were observed during the study, which is ongoing.

Development of mRNA-1944 was supported in part by a grant from the Defense Advanced Research Projects Agency (DARPA) of the U.S. Department of Defense, which has as a priority the development of methods for preventing or stopping infectious disease pandemics.