Researchers from the University of California, Los Angeles — led by Ren Sun, a professor of molecular and medical pharmacology working in the university's David Geffen School of Medicine — came up with a wholly new approach to developing flu vaccines.
As the study authors explain in their new paper, conventional vaccines reduce "immunogenicity" — that is, the ability of a substance to trigger the body's immune response — by attenuating the virus.
But the new approach devised by Sun and his team preserves robust immune responses and works by identifying and eliminating the so-called immune evasion function of the viruses.
Interferons are key
To better understand this, we need to take a look at interferons, which are signaling proteins that coordinate our immune response and are key in fighting off viruses.
The "first-line defense" function of interferons is to neutralize viruses as quickly as possible, while the "second line" of defense is to modulate our immune response, thereby offering us long-term protection against viruses.
As Sun explains, "If viruses do not induce interferons, they will not be killed in the first-line defense; and without interferons, the adaptive immune response is limited."
"For these reasons, viruses have evolved strategies to evade detection and limit the production of interferons by host organisms," he adds.
This results in various pandemics and high numbers of people hospitalized due to influenza-related complications. The Centers for Disease Control and Prevention (CDC) report that, for the 2015–2016 flu season, 310,000 people in the United States were "hospitalized for flu-related illness."
"Because the variations of seasonal influenza viruses can be unpredictable," says Sun, "current vaccines may not provide effective protection against them."
"Previous pandemics and recent outbreaks of avian influenza highlight the need to develop vaccines that offer broader, more effective protection," he adds.
Breaking down the virus's defenses
So, Sun and team examined the genome of the influenza virus in an attempt to find its defense against interferons.
They found and disabled a genomic sequence responsible for so-called interferon induction. "By disabling these interferon-evasion functions," explains first study author Yushen Du, "the engineered virus is weakened in typical hosts."
"At the same time," she adds, "due to interferon stimulation, the engineered virus generates very strong immune responses."
In the video below, the scientists give more details about their vaccine, which will come in the form of a nasal drop:
The researchers also tested the new vaccine in a mouse model and found no significant side effects.
"With this approach, the safety and efficacy requirement of vaccines can potentially be achieved simultaneously. In traditional vaccine development, one is usually sacrificed for the other."
Du explains the new contribution of their study, saying, "Other researchers have knocked out one anti-interferon sequence, but we knocked out eight locations by changing one amino acid at a time."
The next step stemming from this research would be to further test the new vaccine in animals that have two strains of influenza.
Ultimately, the team wishes to put its vaccine forth to the Food and Drug Administration (FDA) for approval, but before this, the vaccine would evidently have to be tested in human clinical trials.
"This approach is also broadly applicable to other pathogens," write the authors.