番茄社区

A single dose of the live-attenuated vaccine candidate VLA1553 for the prevention of disease caused by chikungunya virus produced a strong immune response, a phase III randomized trial showed.

At 28 days post-vaccine, 98.9% of participants in the per-protocol population who received the vaccine had seroprotective chikungunya virus neutralizing antibody levels (95% CI 96.7-99.8, P<0.0001), independent of age, reported Martina Schneider, PhD, the clinical strategy manager at Valneva in Vienna, the company that produces the vaccine, and colleagues.

Adverse events were similar to other licensed vaccines, and VLA1553 was well tolerated by both younger and older adults, they noted in .

"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," Schneider said in a press release. "Our promising results showed good persistence of antibody levels after vaccination, which is important considering that chikungunya outbreaks may recur suddenly."

No significant difference was seen in the seroprotection rate between patients ages 18 to 64 (98.6%) and those 65 and older (100%). At 180 days, 96.3% of those in the VLA1553 arm still had titers above the seroprotective level of antibodies.

"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," Schneider said.

Currently, there is no FDA-approved vaccine for disease caused by the chikungunya virus, an infection that causes fever, joint pain, headache, muscle pain, joint swelling, and rash.

Newborns and older adults are at higher risk for more severe disease, as are individuals with hypertension, diabetes, or heart disease, . Usually it takes about a week for infected patients to feel better, but for some, joint pain has been reported to be disabling, and in some cases persists for several months.

Death is rarely reported, with an estimated case-fatality ratio of 0.3-1 per 1,000 infections. Most deaths are reported in neonates.

"There are several advantages to VLA1553 as a potential chikungunya virus vaccine," wrote Kathryn Stephenson, MD, MPH, of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, in an .

This single-dose vaccine offers immunity within a short time, "an essential benefit given the rapidity of chikungunya virus outbreaks," she noted. What's more, evidence from a phase I trial showed that the vaccine will be durable from one outbreak to another.

However, there are disadvantages to this vaccine, Stephenson pointed out. "Live-attenuated vaccines are typically contraindicated in immunocompromised hosts or during pregnancy. Manufacturing requires growing large quantities of live virus in highly contained and secure facilities, and live vaccines are sensitive to heat and are more difficult to store and ship. For these reasons, other vaccine candidates such as adjuvanted virus-like particle vaccines and inactivated vaccines should continue in development."

Since chikungunya virus outbreaks are unpredictable, the researchers said efficacy trials were not feasible. Both the FDA and the European Medicines Agency gave this trial the go-ahead, using the proportion of baseline negative participants with a seroprotective chikungunya virus antibody level as the primary endpoint, defined as 50% plaque reduction in a micro plaque reduction neutralization test (μPRNT), with a μPRNT₅₀ titer of at least 150 at 28 days after vaccination.

Schneider and team enrolled adults from 43 vaccine trial sites in the U.S. Patients were excluded if they had history of chikungunya virus infection or immune-mediated or chronic arthritis or arthralgia, known or suspected immune system defects, any inactivated vaccine within 2 weeks before vaccination with VLA1553, or any live vaccine within 4 weeks before vaccination with VLA1553.

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 women, 80.4% were white, and 13.9% were Black. Median age was 45, and 11.3% were 65 or older.

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

Participants had their immune responses assessed at 1 week, 28 days, 3 months, and 6 months following vaccination, and adverse events were recorded for 11 days after receiving the vaccine.

Serious adverse events were reported in 1.5% of participants who received the vaccine and 0.8% of participants in the placebo arm. Only two serious adverse events were considered related to VLA1553: one mild myalgia and one syndrome of inappropriate antidiuretic hormone secretion.

Since this study did not take place in an endemic region, where pre-existing immunity may be present, the safety profile in previously infected people is unknown, which was a limitation to the study.

"Determination of contraindications will be subject to agreement between the FDA and the sponsor during the BLA [Biologic License Application] review," Valneva told 番茄社区, adding that a trial in Brazil will be the first in which the vaccine is being studied in an endemic population.

"The most appropriate use for VLA1553 will be determined upon review of these data and in consultation with public health authorities and national immunization technical advisory groups," the company added.

Valneva said they expect the FDA to complete the review by August.

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