Chikungunya virus vaccine candidate is safe and effective

A single dose of live attenuated vaccine candidate VLA1553 to prevent disease caused by Chikungunya virus produced a strong immune response in a randomized phase III trial.

At 28 days post-vaccination, 98.9% of vaccinated protocol adherents had seroprotective chikungunya virus-neutralizing antibody levels (95% CI 96.7-99.8, P.<0.0001) regardless of age, reported Dr. Martina Schneider, clinical strategy manager at Varneva, Vienna, a company that manufactures vaccines, and colleagues.

Adverse events were similar to other licensed vaccines, and VLA1553 was well tolerated by both young and old people, the researchers said. lancet.

“This could be the first chikungunya vaccine available not only for people living in endemic areas, but also for travelers to endemic areas and areas at risk of future outbreaks,” Schneider said. said in a press release. “Our encouraging results showed good persistence of antibody levels after vaccination, which is important considering that chikungunya epidemics can suddenly recur.”

There was no significant difference in seroprotection rates between patients aged 18-64 years (98.6%) and those aged 65 years or older (100%). At 180 days, 96.3% of the VLA1553 group still had titers above antibody seroprotective levels.

“Since age is a risk factor for chikungunya severity and mortality, the strong immune responses observed in older participants may be particularly beneficial,” Schneider said.

There is currently no FDA-approved vaccine against the illness caused by the Chikungunya virus, which causes fever, joint pain, headache, muscle pain, swollen joints, and rash.

Newborns and the elderly are at increased risk of more serious illness, as are people with high blood pressure, diabetes, and heart disease. According to the CDC. It usually takes about a week for infected patients to feel better, but some patients report disabling joint pain, which can persist for months. I have.

Few deaths are reported, with an estimated fatality rate of 0.3 to 1 per 1,000 infections. Most deaths have been reported in neonates.

“VLA1553 has several advantages as a candidate chikungunya virus vaccine,” writes Kathryn Stevenson, M.D., MPH, Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston. Accompanying editorial comment.

The single-dose vaccine confers immunity in a short period of time, “a vital advantage given the speed of the Chikungunya virus epidemic,” he said. Furthermore, evidence from Phase 1 trials showed that this vaccine was durable from outbreak to outbreak.

But the vaccine also has drawbacks, Stevenson said. “Live-attenuated vaccines are generally contraindicated in immune-compromised hosts and during pregnancy. It is weaker and more difficult to store and transport.For these reasons, other vaccine candidates such as adjuvanted virus-like particle vaccines and inactivated vaccines should also continue to be developed.”

The researchers said efficacy trials were unfeasible because chikungunya virus epidemics are unpredictable. Both the FDA and the European Medicines Agency have identified this as the primary endpoint, the proportion of baseline-negative participants with seroprotective chikungunya virus antibody levels defined as 50% plaque reduction in the microplaque reduction neutralization test (μPRNT). I gave the green light to the exam. ), using μPRNT₅₀ A titer of at least 150 at 28 days post-vaccination.

Schneider and team enrolled adults from 43 vaccine clinical trial sites in the United States Patients with chikungunya virus infection, immune-mediated or chronic arthritis or joint pain, known or suspected immune system defects, 2 weeks prior to vaccination Prior history of inactivated vaccine was excluded. VLA1553, or a live vaccine within 4 weeks prior to VLA1553 vaccination.

From September 2020 to April 2021, 4,128 participants were enrolled and randomized 3:1 to VLA1553 or placebo.

The safety population included 4,115 participants (3,082 in the VLA1553 group and 1,033 in the placebo group). 54.7% were female, 80.4% were white, and 13.9% were black. The median age was 45 years, and 11.3% were 65 years or older.

The population per protocol included 362 participants (266 in the VLA1553 group and 96 in the placebo group).

Participants were assessed for immune responses 1 week, 28 days, 3 months, and 6 months after vaccination, and adverse events were recorded for 11 days after vaccination.

Serious adverse events were reported in 1.5% of vaccinated participants and 0.8% of placebo participants. He had only two serious adverse events considered to be related to VLA1553, one of mild myalgia and one of inappropriate antidiuretic hormone secretion syndrome.

The study was not conducted in an endemic area where pre-existing immunity might exist, so the safety profile in previously infected people was unknown, which was a limitation of the study.

“Determination of contraindications is based on agreement between the FDA and the sponsor during the BLA period. [Biologic License Application] Please review it,” said Varneva. Today’s MedpageHe added that the trial in Brazil would be the first time the vaccine has been studied in populations of endemic areas.

“The most appropriate use of VLA1553 will be determined by reviewing these data and in consultation with public health authorities and national Immunization Technical Advisory Groups,” the company added.

Valneva said he expects the FDA to complete its review by August.