Chikungunya virus is spread through infected Aedes aegypti and Aedes albopictus mosquitoes—the same mosquitoes that transmit dengue and Zika virus. Endemic in Africa and parts of Asia, outbreaks of the virus have occurred more recently in Europe and the Caribbean with local transmission in North America documented in 2013. Additionally, Chikungunya is one of the viruses most likely to spread globally due to climate change’s effects on the spread of mosquitos.
Chikungunya is an alphavirus (belonging to the family Togaviridae) that causes a fever and severe muscle and potentially debilitating joint pain roughly four to eight days after infection. The joint pain may be prolonged, lasting for weeks, months, or even years. Serious disease and death are rare, but older people and newborn babies are at higher risk.
Currently, there are no approved vaccines to prevent Chikungunya. The prevention strategy is the same recommended for other mosquito borne-illnesses: try to prevent mosquito bites by wearing repellent, long sleeves, and going indoors.
Now, a live-attenuated vaccine candidate (VLA1553) shows promising results in a Phase III randomized controlled trial, reporting safety and immunogenicity data up to 180 days after vaccination. The VLA1553 vaccine candidate was generally well tolerated and produced an immune response in 99% (263/266) of participants after a single injection. There was no difference in immune response according to age.
This work is published in The Lancet, in the paper, “Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicenter, randomized, placebo-controlled, Phase III trial.”
“This could be the first chikungunya vaccine available for people living in endemic regions, as well as for travelers to endemic areas or areas at risk for an upcoming outbreak,” Martina Schneider, PhD, clinical strategy manager at Valneva. “Our promising results showed good persistence of antibody levels after vaccination, which is important considering that chikungunya outbreaks may recur suddenly. As age is a risk factor for severity and mortality of chikungunya disease, the strong immune response observed in older participants might be particularly beneficial.”
Because the study, VLA1553-301, was not conducted in regions where chikungunya is endemic, researchers were unable to investigate whether the vaccine protects against subsequent disease. Instead, the study tested for an immune response at levels that are thought to protect against the disease if infected with the virus.
The study enrolled 4,115 healthy adults across 43 study sites in the United States. 3,082 participants were given one dose of VLA1553 (via an injection in the arm), and 1,033 were given a placebo. All participants were included in the safety analysis but the immune response was only tested in a subgroup of 362 participants (266 given the vaccine and 96 given the placebo). Participants had their immune responses assessed one week, 28 days, three months, and six months after their vaccination. They also recorded adverse events in an electronic diary for 11 days after vaccination. Those who did experience adverse events within 21 days of vaccination (e.g., fever and joint pain, back pain, neurological symptoms, heart problems, rash, or swelling) were monitored more closely.
VLA1553 was generally well tolerated across all age groups with most adverse events (AE) being mild or moderate. In those given the vaccine, the most common adverse events were headaches (experienced in 32% of vaccinated participants), fatigue (29%), muscle pain (24%), joint pain (18%), and pain at the injection site (13%). After six months, there were more adverse events recorded for those given VLA1553 than for those given placebo. Overall, 51% of participants who were given VLA1553 and 31% of those who received the placebo experienced at least one AE that was considered related to the vaccination.
Serious adverse events were reported in 2% of participants exposed to VLA1553 and 1% of participants in the placebo arm. Two of these were classified as related to the vaccine.
The authors noted some limitations of their study. The vaccine is made from a weakened version of the live virus, so is likely to be unsuitable for people with weakened immune systems, and pregnant women. They also acknowledge that to be highly effective in controlling endemic disease, a chikungunya vaccine will also need to be administered to children. To determine safety and efficacy in this age group, there is a study in adolescents in endemic areas of Brazil currently ongoing.