The first vaccine against the mosquito-borne viral disease chikungunya will likely come to market next month. With the debilitating disease now afflicting more than half the countries in the world and threatening to spread further, the imminent U.S. Food and Drug Administration (FDA) approval of the vaccine is “great news,” says Scott Weaver, a virologist at the University of Texas Medical Branch whose own lab started to work on a chikungunya vaccine nearly 2 decades ago.
The vaccine, made by the French company Valneva, will likely be recommended mainly to U.S. travelers at first. But many expect an FDA approval will also grease the wheels for the vaccine to become available in the most affected countries.
First documented in 1952 in modern-day Tanzania, chikungunya means “disease that bends up the joints” in Kimakonde, an East African language. Although rarely fatal, chikungunya virus causes long-term, debilitating joint pain in up to 40% of people it infects, most of whom live in warm climates that have large populations of two mosquito species, Aedes aegypti and A. albopictus. Almost all cases in the United States have been in travelers who have returned from affected countries.
The vaccine consists of a lab-weakened version of the virus that does not cause disease, and it is likely to be approved without the usual efficacy data from human trials. FDA agreed with Valneva—and wide consensus in the field—that a standard efficacy trial comparing rates of disease in people who receive the vaccine versus dummy shots was not feasible. “The virus spreads tremendously fast,” leaving too little time to launch and complete a trial, says Barbara Schnierle, a virologist at the Paul Ehrlich Institute who studies chikungunya. (Schnierle advises the European Medicines Agency about HIV vaccines but is not involved with Valneva’s application there.) “Logistically, you will never be able to do a normal phase 3 study.”
Valneva instead staged studies that showed 99% of people who received a single shot developed long-lasting antibodies that could neutralize the virus in test tubes. The company went on to show that when it infused monkeys with these antibodies and then gave them the virus, the animals controlled viral levels and did not develop any symptomatic disease. If the vaccine wins approval, FDA will require Valneva to conduct a postmarket study in humans to evaluate whether it actually protects against disease in the real world.
Valneva’s expected approval comes after years of frustratingly slow progress. More than 5 decades ago, the U.S. Army made a chikungunya vaccine that protected monkeys and even entered a small human trial, but the military saw little need for it and didn’t advance the research. Other efforts similarly languished, in part because at the time, the disease surfaced only sporadically in a few African and Asian countries.
In 2004, Kenya had the world’s first documented large-scale outbreak of chikungunya in 30 years. The next year, a large outbreak hit Réunion Island, an overseas territory of France in the Indian Ocean that had never detected a case. Estimates suggest nearly 40% of the population was infected, and 85% of people developed debilitating symptoms.
Analyses of the circulating virus showed it had mutated to allow replication in the A. albopictus mosquitoes, which have a different range from its original host, A. aegypti. The virus also became better at copying itself in both species, increasing transmission to humans. Outbreaks soon exploded in India, Thailand, the Caribbean, and Brazil. Chikungunya did so well that in many locales, it bumped out dengue virus, which the same mosquito species transmit. To date, more than 100 countries have reported local transmission of the virus. “It just took over entire mosquito populations and caused large outbreaks,” says virologist Timothy Endy, who heads a chikungunya vaccine program at the Coalition for Epidemic Preparedness Innovations (CEPI), a nonprofit that provides funding to Valneva and other developers.
Serious interest in vaccines finally ramped up—including the one made by Valneva, which it licensed from a group at the Karolinska Institute. An inactivated virus candidate from India’s Bharat Biotech, which may be safer for pregnant and immunocompromised people, is close on the heels of the Valneva shot.
Last week, a chikungunya vaccines working group that advises the Centers for Disease Control and Prevention (CDC) recommended the Valneva shot primarily be offered to U.S. adults who will be visiting countries that have active outbreaks. Travelers older than 65 or with preexisting medical conditions that might make them more susceptible to severe disease also “may be considered” for a vaccine if they are visiting a country that had an outbreak within the past 5 years, CDC’s Advisory Committee on Immunization Practices (ACIP) said. Also eligible: people staying in endemic countries for at least 6 months and lab workers who handle the virus as part of their research. Endy, a U.S. Army researcher for 24 years, suspects the military will recommend the vaccine for its members traveling to affected areas, because chikungunya could “bring battalions down.”
Now, “We need to invest in the appropriate conversations and regulatory approvals” to make the vaccine available to people beyond wealthy travelers, Endy says. Among the countries that could really use the vaccine are Brazil and Paraguay, which together have seen 75% of the world’s 440,000 reported chikungunya cases this year. With CEPI’s help, Brazil’s Butantan Institute is now partnering with Valneva to bottle the vaccine and make it affordable there and to other middle- and low-income countries. At the ACIP meeting, a Valneva representative said it will likely sell for about $350 a dose to U.S. travelers. Although the discounted price has yet to be determined, Endy expects it will be about $10 to $20 per dose.
Climate change may make chikungunya vaccines even more important. Warming climates are altering mosquito populations, which Schnierle notes are already moving north in Europe. “We’ve had local outbreaks in Italy, Spain, and France from travelers coming back from tropical countries,” Schnierle says. “Climate change will change the whole situation.”
