Chikungunya Vaccine Trial Shows Promise

By Vidya Shankar

NEW YORK (Reuters Health) - A live recombinant vaccine against chikungunya infection, produced by modifying the measles vaccine virus, was safe and induced a good immune response in healthy volunteers in a new study from Austria.

The research team hopes the vaccine will be available for adults and children in four to six years, corresponding author Dr. Erich Tauber, chief executive officer, Themis Bioscience, told Reuters Health by email.

Chikungunya fever is a mosquito-borne arbovirus infection that can result in chronic debilitating arthritis. It occurs as outbreaks in tropical countries, but is becoming a global threat due to travel and global warming. Currently there are no treatments or vaccines, the researchers noted online March 2 in Lancet Infectious Diseases.

The experimental vaccine was produced by introducing Chikungunya virus genes into the Schwartz strain of measles vaccine.

From November 2, 2013 to February 5, 2014, the researchers enrolled 42 healthy adults from Vienna ages 18 to 45. Twelve volunteers each received either the low, medium, or high dose of the experimental Chikungunya vaccine. Six controls received the measles, mumps rubella vaccine (Priorix).

A booster dose of the same was then given on either day 28 or 90. Those who received the vaccine on day 28 received a saline placebo injection on day 90 and vice versa. Blood samples were collected for antibody titers using the plaque reduction neutralization tests (PRNT) prior to each dose, on day 56, and 30 days after last dose.

Geometric mean titers (GMT) of 10 or more were considered protective against Chikungunya. Measles antibody titers were also tested alongside to evaluate the impact of pre-existing anti-measles antibodies on Chikungunya immunity. Participants kept a record of any side effects occurring within two weeks of vaccination.

Schwartz measles vaccine was chosen as the vector because it is one of the "safest and most efficient human vaccines," and is easily amenable to genetic manipulation, the researchers said.

After the first dose of the Chikungunya vaccine, the seroconversion rates were 44%, 92% and 90% in the low-, medium- and high-dose groups, respectively, and increased to 100% in all groups after the booster dose, the researchers report. The average GMTs were significantly greater in the medium- and high-dose vaccine groups as compared to the low-dose group. Pre-existing measles antibodies did not affect the immune response.

Significant adverse events including headaches, musculoskeletal pain, nasopharyngitis, and local reactions were reported in six volunteers. Side effects were more common with higher vaccine doses.

"The medium vaccine dose might have yielded the best ratio of immunogenicity to tolerability," the researchers point out.

Chikungunya spreads rapidly with high attack rates, said Dr. Suresh Mahalingam from the Griffith University, Queensland, Australia, in email to Reuters Health. Dr. Mahalingam, who wrote an accompanying editorial, said infants, the elderly, and tourists to endemic areas are particularly susceptible and most in need of the vaccine.

"It is possible that the capricious nature of Chikungunya epidemics may pose a problem," Dr. Mahalingam pointed out. "The challenge is to get industries such as biotechnology companies and big pharma to invest in the development of these vaccines," he said.

Larger trials are required involving population at risk living in endemic areas, the researchers concluded.

This study was funded by Themis Bioscience GmBH, which employs three of the study authors.

SOURCE: https://bit.ly/1b6at6Z

Lancet Infect Dis 2015.

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