UCLA charts progress in the search for a more effective flu vaccine

Vaccine
The holy grail of flu-vaccine development is a universal vaccine that would offer protection against many different strains of the virus.

This is one of the worst flu seasons on record, with the proportion of deaths attributed to the virus running above average, according to the Centers for Disease Control. Ten children died of the flu in the week ended Jan. 13 alone, the agency reported. One of the culprits is this year’s seasonal flu vaccine, which is providing inadequate protection against the most recently reported strain of the virus.

Scientists at the University of California in Los Angeles are working on a new approach to developing flu vaccines that they believe could provide better protection against the virus. What’s more, they hope their approach could result in a nasal spray that people could use to vaccinate themselves at home.

The approach revolves around understanding how the flu virus interacts with the immune system—specifically with immune proteins called interferons. Viruses typically devise survival strategies by limiting interferon production, said Ren Sun, professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA, in a statement. Sun’s team spent four years scrutinizing the influenza genome, searching for genes that give the virus this power to block interferon.

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The UCLA team then deactivated amino acid sequences that are involved in evading interferon, according to a statement. The resulting virus had a weakened ability to infect its host, but the resulting stimulation of interferon generated a strong immune response, Sun said. The research was published in the journal Science.

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Disabling genetic sequences in the flu virus is not a new idea, said the study’s first author, Yushen Du. But the UCLA team was able to generate broader protection than other teams had achieved, they reported. “Other researchers have knocked out one anti-interferon sequence, but we knocked out eight locations by changing one amino acid at a time,” Du said in the statement.

The main problem with the existing flu vaccine is that it must be developed many months before the start of flu season, when it can be hard to identify which strains will become most prevalent. Furthermore, the virus mutates so quickly that the vaccine has to be reformulated every year. That’s why the holy grail of flu-vaccine development is a universal vaccine—one that would work in everybody regardless of which strain is circulating in any particular year.

Several approaches to developing a universal flu vaccine are being investigated. In 2016, for example, SEEK Group and hVIVO launched a startup, Imutex, to develop a flu vaccine that works by zeroing in on proteins that all flu viruses possess. And last year, scientists at the National Institutes of Health announced they are investigating an approach that involves targeting the “stem” domain of the flu virus, which is a region of the virus that doesn’t change drastically from season to season.

The next step for the UCLA researchers is to test their vaccine in animal models of two strains of flu. From there, they hope to move to clinical trials in people. They aim to formulate the vaccine into a nasal spray, which they believe will not only be more convenient for patients but could also cut down on the overall cost of vaccinating the public.