Thursday, September 24, 2020

Why vaccines need to be well tested

Vaccines have saved many lives.  Before we had them, half of all children died before puberty.  Smallpox, polio, and other infections killed many.  Flu vaccine saves many lives  But there have also been cases where vaccines turned out to have unexpected problems.  The first widely used vaccine for dengue fever shows why vaccines need to be well tested before widespread use.

A new dengue vaccine shows promise — at least for now

By Aimee Cunningham
November 6, 2019 at 5:19 pm

The latest dengue vaccine reduced the occurrence of the disease by about 80 percent in children vaccinated compared with unvaccinated children, researchers report. But the full picture of the vaccine’s safety and effectiveness is still under study, and won’t emerge for several more years. 


But creating a vaccine against dengue is challenging. There are four different, but closely related, dengue viruses, labeled by number. A person infected by dengue type 1, for example, develops antibodies to that type. But those antibodies can conspire to make a second infection with a different dengue virus severe (SN: 11/8/17).

This phenomenon, called antibody-dependent enhancement, “plagues vaccine development,” says Scott Halstead, a virologist who has spent his career studying dengue and first described this enhancement in the 1960s. If a vaccine doesn’t produce a strong and long-lasting immune response to all four of the viruses, it could mean a later infection not only isn’t protected against, but is actually made worse.

That’s what happened with the first widely used vaccine candidate, Dengvaxia, developed by the pharmaceutical company Sanofi Pasteur, based in Lyon, France. In a 2015 study, researchers reported the vaccine reduced the occurrence of dengue by around 60 percent in vaccinated children. But in 2017, the company announced the vaccine shouldn’t be used in children who hadn’t been previously exposed to dengue. A huge vaccination campaign in the Philippines was halted, and reports surfaced of some children becoming very ill after vaccination (SN: 5/21/19).

“The vaccine was acting as a silent first infection in those kids who hadn’t been exposed in the past,” says infectious disease epidemiologist Isabel Rodriguez-Barraquer of the University of California San Francisco School of Medicine, who was not involved in the development of either vaccine. After reanalyzing the data from the Dengvaxia clinical trials, scientists reported that the vaccine protected kids who already had been exposed to dengue, but increased the risk of severe infections in kids who hadn’t been, according to a study published July 2018 in the New England Journal of Medicine.

Going forward, it will take a lot of transparency from vaccine manufacturers and questioning from the scientific community “to make sure that the same thing doesn’t happen again,” Rodriguez-Barraquer says. “I do hope eventually there will be a dengue vaccine that will be accepted,” she says. “It would help a lot of people.”


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