Chikungunya vaccine looks promising in phase 1 trial

A chikungunya vaccine based on a weakened measles virus looked promising in a phase 1 trial, with most recipients developing neutralizing antibodies after one dose, according to a report published today in The Lancet Infectious Diseases.

Meanwhile, the Pan American Health Organization (PAHO) reported over the weekend that the chikungunya count in the Americas edged upward by about 2,800 cases in the preceding week, to 1,250,895, a much smaller increase than the week before.

Third vaccine tested

The chikungunya vaccine was developed by Themis Bioscience Gmbh, based in Vienna, which funded the study. It is only the third chikungunya vaccine to reach clinical trials, according to the report and an accompanying commentary by a pair of Australian experts.

The vaccine is based on an attenuated measles vaccine virus known as the Schwarz strain, which is described in the commentary as a good choice because it is safe and has been mass-produced at low cost since the 1960s.

The study was conducted by researchers from Themis Bioscience and collaborators from the University of Vienna and from France and the United States. They randomly assigned 42 volunteers to receive a low, medium, or high dose of the chikungunya vaccine or Priorix, a vaccine for measles, mumps, and rubella that contains the Schwarz strain of measles virus.

The chikungunya vaccine recipients were randomly assigned to receive a second dose of the vaccine either 28 or 90 days after the first dose. The primary outcome measured was the presence of neutralizing chikungunya antibodies 28 days after the first dose (defined as seroconversion), as assessed by a reduction in the number of virus plaques in infected Vero cells by at least 50%.

The chikungunya vaccine groups numbered 12 people each, while 6 received Priorix; a total of 36 volunteers completed the trial. After one dose of the candidate vaccine, neutralizing antibodies were detected in 44% (4 of 9) recipients in the low-dose group, 92% (11 of 12) in the medium-dose group, and 90% (9 of 10) in the high-dose group. All of the recipients had neutralizing antibodies after the second dose of vaccine.

No measles interference

The researchers determined that the volunteers' preexisting measles antibodies did not interfere with immune response to the vaccine, but they note that this finding will need to be confirmed in larger studies.

On the safety side, there were seven severe adverse events in six volunteers, including headache, fever, and injection-site reactions. Two of the adverse events were unrelated to vaccination.

The authors say their study marks the first time that a vaccine based on a measles virus has been shown to induce neutralizing chikungunya antibodies in healthy adults, including those with immunity to measles.

In the editorial, Penny A Rudd, PhD, and Suresh Mahalingam, PhD, of the Institute for Glycomics at Griffith University's Gold Coast Campus in Queensland, Australia, cite as important the finding that measles antibodies did not reduce the vaccine's immunogenicity, given the high measles vaccination coverage around the world.

The writers express some caution about the vaccine's safety, since six (17%) volunteers had severe adverse events. "Despite the generally acceptable tolerability profile, one in six patients is a fairly concerning figure and this aspect will need to be carefully followed up in future trials," they said.

The pair observe that two other experimental chikungunya vaccines reached clinical trials, and both were shown to induce immune responses with few adverse effects. One vaccine, which used a live-attenuated chikungunya virus, reached the phase 2 stage but fell victim to a lack of funding. They said the status of the other one, involving a virus-like-particle, is unclear.

Although it takes a long time to get a vaccine licensed, they conclude, "With two potential candidates in the pipeline, we might be on the right track in the fight against chikungunya."

Case count tops 1.25 million

Meanwhile, PAHO's Feb 27 count of chikungunya cases in the Americas, at 1,250,895, is up by 2,802 since a week earlier. The new total includes 1,222,418 suspected and 24,982 confirmed cases, all locally acquired, plus 3,495 imported cases.

Jurisdictions that reported increased cases included El Salvador, up by 1,383 at 143,172; Honduras, up 1,556 at 6,908; and Puerto Rico, up 1,700 at 30,747.

At the same time, Brazil slashed its case count by 2,627, to 4,116, by eliminating most of the 2,776 confirmed locally acquired cases it had reported previously. The report offered no explanation for the change.

The United States added 18 imported cases to its chikungunya count, for a total of 2,535 cases, with 11 locally acquired ones and the rest imported.

The death toll for the epidemic stayed the same, at 183.

Ramsauer K, Schwameis M, Firbas C, et al. Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial. Lancet Infect Dis 2015 (early online publication Mar 1) [Abstract]

Rudd PA, Mahalingam S. Fighting back against chikungunya. (Commentary) Lancet Infect Dis 2015 (early online publication Mar 1) [Extract]

See also:

Feb 27 PAHO update

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