Chikungunya vaccine provokes immune response in phase 3 trial

A vaccine candidate for chikungunya disease, produced by Valneva, has been found to produce an immune response in 99% of phase 3 trial participants. The study tested for an immune response at levels that are thought to protect against the disease if infected, with the results published in The Lancet.

Chikungunya is a mosquito-borne disease caused by the chikungunya virus (CHIKV), which is endemic in some regions of Africa, Asia and the Americas. It causes a fever in patients roughly four to eight days after they have been bitten by an infected mosquito, with older people and newborn babies most at risk. Symptoms include headaches, fatigue, nausea, and severe muscle and joint pain; the joint pain is often debilitating and lasts anywhere from days to years. Currently there are no approved vaccines to prevent the disease caused by CHIKV infection, nor are there effective antiviral treatments for the disease — and with climate change driving the spread of the mosquitos that carry it into new areas of the world, an effective vaccine would be key to helping to prevent future outbreaks.

The new study enrolled 4115 healthy adults across 43 study sites in the United States. 3082 participants were given one dose of the vaccine VLA1553 (via an injection in the arm), and 1033 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.

After a single vaccination, VLA1553 induced antibody levels at a level that is considered to protect against disease among 99% (263/266) of participants, with no difference in immune response according to age. It was also generally well tolerated across all age groups, with most adverse events 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%). There were more adverse events recorded for those given VLA1553 than those given placebo.

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 — one was a case of mild muscle pain in a woman with a medical history of fibromyalgia, and the other was a fever that resulted in hospitalisation. The rate of observed miscarriages in the population given VLA1553 was also slightly higher than expected in the general population (23% versus around 11–16%), but this could be due to natural variation in the small sample size. Two of the three miscarriages among women given VLA1553 were explained by genetic disorder or the participants’ history of miscarriage; in the remaining case, no reason could be identified and the authors acknowledge that further monitoring will be needed as the vaccine candidate is rolled out.

“An independent Data Safety Monitoring Board (DSMB) evaluated safety data during the study and did not identify any safety concerns after evaluating all reported adverse events,” said Dr Juan Carlos Jaramillo, Chief Medical Officer at Valneva. “The two related serious adverse events reported during the study both recovered fully and were reviewed by the DSMB, who did not raise concerns or consider that there were serious risks caused by the vaccination in general.”

The authors note some limitations of their study. The study was not conducted in regions where chikungunya is endemic, so 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. Furthermore, participants’ pre-existing immunity to the chikungunya virus remains unknown, as does the safety of the vaccine in this population.

As the vaccine is made from a weakened version of the live virus, it is likely to be unsuitable for people with weakened immune systems and pregnant women. Furthermore, in order to be highly effective in controlling endemic disease, a chikungunya vaccine will 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.

“This could be the first chikungunya vaccine available for people living in endemic regions, as well as for travellers to endemic areas or areas at risk for an upcoming outbreak,” said lead author Dr Martina Schneider, 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.”

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