Single antiviral shot could offer better protection than flu vaccines

A single dose of a long-lasting antiviral drug has shown promise in protecting against all flu strains, raising hopes that it could protect those who are most vulnerable.

The flu kills thousands of people every year and the rapid evolution of new variants could trigger the next pandemic. Each year, scientists update flu vaccines to match the strains of influenza virus they expect to circulate most widely during the upcoming flu season. These vaccines prompt the immune system to produce antibodies that stop the virus from entering your cells.

Scientists are working towards a universal flu vaccine that would protect against all strains that infect people, but such a vaccine would still have limitations.

“Even if someone came up with the first [approved] universal flu vaccine, it is never going to protect everyone, because people have various degrees of immune response to vaccines,” says Jeffrey Stein, CEO at biotech company Cidara. For instance, vaccines are generally less effective in older people or those with suppressed immune systems.

To address this, Stein and his colleagues developed a treatment called CD388, which contains zanamivir, an antiviral drug that is approved for treating infections caused by all flu strains that infect people. Zanamivir is usually cleared from the body within hours, but the team chemically modified it to linger for months in the body, where it can rapidly destroy invading flu viruses. “It doesn’t engage the immune system,” says Stein.

To put it to the test, the team recruited 5000 people, aged 16 to 64, from the US and the UK at the start of the 2024 flu season. None of the participants was at high risk of flu-related complications or had yet received a flu vaccine that year. The team split the participants into four roughly equal groups. Three received a single injection of CD388 at either a low, medium or high dosage, while the remaining participants took a placebo.

About six months later, the researchers looked at how many participants had symptomatic flu infections over the entire flu season – defined by the presence of flu virus DNA in nasal swabs, plus flu-like symptoms such as a cough and a fever.

While 33 people in the placebo group had symptomatic flu, only eight people who took a high dose of CD388 did – about a 76 per cent reduction in risk. Those in the medium- and low-dose groups saw their risk of symptomatic infection cut by 61 per cent and 58 per cent, respectively. “All doses demonstrated significant protection against influenza illness,” says Nicole Davarpanah, chief medical officer at Cidara. Similar side effects, such as tenderness at the injection site, occurred across the treatment and placebo groups.

The findings suggest CD388 could offer a simpler way to protect people than vaccines. “[Unlike vaccines, it] would not need to be matched to circulating strains and might be more effective in ‘poor match’ years or as part of pandemic preparedness should a novel influenza strain, such as H5N1 strains, move into humans,” says Penny Ward at King’s College London. Based on prior data on zanamivir, flu strains are also unlikely to evolve resistance to it, she says.

Crucially, the approach should work well in people known to respond poorly to vaccination, such as older people or the immunocompromised, as it doesn’t rely on the host immune response, says Ward. To explore this, Davarpanah says the team is planning a trial in immunocompromised people aged 12 and above.

Stein says that, rather than replace vaccines, the drug may work best in conjunction with them – though this has yet to be tested. Still, the results are timely amid rising scepticism of vaccines. “It avoids the controversy that is unfortunately now associated with vaccines,” says Stein.