The Chase For A Permanent Flu Vaccine

The Chase For A Permanent Flu Vaccine.

As doctors struggle with the worst flu season in nearly a decade, some are racing to answer a question: Can they find a more permanent solution than variably successful annual vaccines? Researchers at the University of California, Los Angeles have developed a new approach for a vaccine that tested successfully in animals. GlaxoSmithKline is in the early stages of testing another promising approach in people. And the newly launched Universal Influenza Vaccine Initiative is sequencing the blood of individuals who receive the current flu vaccine or are infected with the virus. The group hopes to shed light on the body’s immune response to ultimately develop better treatments.

The development of a universal influenza vaccine that would protect against multiple strains of the flu is a priority, says Anthony Fauci, director of the federal National Institute of Allergy and Infectious Diseases. But it’s many years away from becoming a reality. “There are about a dozen candidates that range from preclinical animal studies up through and including phase-two clinical trials,” he says. “But we’re still in the area of scientific discovery.” Combating the flu is difficult for some reasons. Humans are infected by influenza A or B viruses. Mutations can create different strains among the main two types of A viruses infecting humans, H1N1 and H3N2. Scientists must make an educated guess months ahead of time on which strains they expect to circulate the following flu season, because of the time required to make the vaccine. But the virus can mutate in that time, resulting in a mismatch between the circulating virus and the vaccine. This year’s dominant flu type—H3N2— tends to mutate or change, making the vaccine less effective. It also causes a greater number of hospitalisations and deaths than other strains. In any year, the vaccine reduces the risk of contracting the flu by about 40% to 60%. In years where the H3N2 is dominant, the numbers are usually lower. That could help explain why less than half of adults in the U.S. usually get the vaccine. Doctors urge everyone over six months old to get it, noting that even if you contract the flu, the shot will make the virus less severe and shorten the time you are sick.

Still, there are those like Adam Hirsch who don’t. The 40-year-old New York City resident, who works in the financial industry, says he’s never received a flu vaccine. Neither has his wife. “It’s not very effective,” Mr Hirsch says. “We don’t think it works.” This year they got one for their 19-month-old daughter late in the season only because of all the news about hospitalisations and deaths. “We didn’t get it for her last year, and when she’s a little bit older, I don’t think we would do it,” he says. If a vaccine had a higher success rate, he would get it. Scientists are a long way off from better rates of protection, but there are glimmers of hope.

UCLA researchers tested a vaccine in ferrets and mice that boosted their immune systems’ ability to fight many viral strains. The study was published in January in Science. The vaccine is “live”—consisting of a weakened form of the virus—and therefore triggers a response from B and T cells, which are both white blood cells that fight viruses, says Ren Sun, a professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and senior author of the study. When developing the vaccine, researchers focused on interferons, proteins the body creates to kill viruses and trigger a successful immune response. Current flu strains feature functions that evade those interferons. The researchers identified these functions and deactivated them, developing a flu strain that counteracted their effects. Dr Sun says that if the virus cannot escape the interferons, two things happen: “One, the interferon system limits the virus replication. Two, strong interferon production stimulates a stronger antibody and T cell response.” The test virus protected animals against the H3N2 and H1N1 strains of influenza. The experiment needs to be repeated with influenza B strains, which are very different, says Dr Sun.

Peter Palese and co-researchers have developed a different approach to a universal flu vaccine that’s being tested in two phase one clinical trial in humans. GlaxoSmithKline is conducting one trial, and the Bill & Melinda Gates Foundation is spearheading the other. The vaccine they developed focuses on hemagglutinin, a protein that helps the flu virus bind to certain cells in the body, such as those in the upper respiratory tract. Part of the protein doesn’t change from year to year, says Dr Palese, a microbiologist at the Icahn School of Medicine at Mount Sinai in New York City. The idea is to redirect the immune system to target those unchanging regions, he says. Researchers hope this creates a vaccine that works against all flu strains. The proposed vaccine succeeded in animal experiments, working against all influenza A and B strains tested.

James Crowe, director of the Vanderbilt Vaccine Center, is leading the Universal Influenza Vaccine Initiative, a global effort to develop a vaccine. The project is examining babies, pregnant women, adults and the elderly to see how their first exposure to the flu impacts responses to future vaccines and viruses. The initiative also uses DNA sequencing technology to decode billions of antibody and T cell sequences as they occur in humans. Researchers are getting blood samples from people either after they get the flu vaccine or just after they are infected with the virus and sequencing their blood for antibody and T cell responses. They have 60 people enrolled in the study, with the goal of sequencing 1,000.

Credit: Sumathi Reddy for The Wall Street Journal, 5 February 2018.