Experimental Chikungunya Vaccine is Safe and Well-Tolerated in Early Trial

An experimental chikungunya vaccine has been shown to be both safe and confer durable immune responses in healthy volunteers, researchers report in a paper published this week in The Journal of the American Medical Association (JAMA). Researchers from NIAID led the trial, which enrolled 400 adults ages 18 to 60 at six sites in Puerto Rico, Haiti, the Dominican Republic, Martinique, and Guadalupe from November 2015 to March 2018. The vaccine, which was developed by scientists at NIAID’s Vaccine Research Center (VRC), generates an immune response to chikungunya virus for at least sixteen months after vaccination. Additional research is needed to determine if the vaccine can effectively prevent chikungunya virus infection.

The chikungunya virus can be transmitted by the bite of an Aedes mosquito. Not all people with chikungunya infections experience symptoms; however, many people develop a fever, which can be accompanied by severe headaches, nausea, fatigue, rashes and extremely painful joint inflammation. The pain can last for weeks, or even months, after the initial infection, and there are no approved drugs to treat the infection—or any vaccines which can prevent it. To date, the most effective measures against chikungunya have relied upon mosquito control and protecting people from mosquito bites.

There are three known types of chikungunya virus; however, all three types share characteristics that a single vaccine could target. The virus is a relative newcomer to the Americas: Although chikungunya had previously been detected in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans, local transmission of the virus was first detected in the Caribbean in 2013. Since then, the virus has spread throughout most of the Americas, including the United States.

The chikungunya vaccine candidate being tested in this trial, known as CHIKV VLP, contains virus-like particles (VLPs), which are manufactured in mammal cells. These VLPs contain chikungunya virus structural proteins, which the human immune system can learn to recognize. However, because they do not contain any genetic material from the virus, VLPs cannot replicate and cause chikungunya infection. However, they can generate potent immune responses. Other vaccines using VLPS have previously been approved by the FDA, including vaccines for hepatitis B and human papillomavirus. The new chikungunya VLP vaccine was developed by researchers at the VRC was previously tested in a small Phase 1 trial. These results suggested that the vaccine was safe, would likely produce potentially protective immune response to the chikungunya virus.

Julie Ledgerwood, D.O. and Grace Chen, M.D., from NIAID’s VRC were study co-chairs for the Phase 2 trial. The study enrolled participants in regions where chikungunya is already present, so prospective volunteers were screened in an effort to enroll those not previously infected with chikungunya. Four hundred healthy adult volunteers were randomly assigned to receive either two 20-microgram doses of the vaccine, or two placebo injections. The injections were given 28 days apart. The volunteers participated in study visits for 72 weeks after the first injection to monitor for adverse effects and to assess the vaccine’s ability to induce a lasting immune response in blood samples.

After analyzing the results, the researchers concluded that the vaccine was both safe and well-tolerated. None of the volunteers experienced serious adverse effects that were related to the vaccine. In addition, the volunteers that received the vaccine developed an immune response to the chikungunya virus that remained strong for the entire 72 weeks of the study. These results support the conclusions of an earlier, smaller trial of the vaccine. NIAID has granted nonexclusive rights to develop and commercialize the CHIKV VLP vaccine to several organizations.

For more information about the trial, visit ClinicalTrials.gov and search identifier NCT02562482.

Reference:  G Chen et al. Effect of a chikungunya virus-like-particle vaccine on safety and tolerability outcomes: a double-blind randomized clinical trial. The Journal of the American Medical Association. DOI: 10.1001/jama.2020.2477. (2020)