Getting a flu shot is an unpleasant annual routine for many people, but the virus’ tendency to constantly evolve makes it a necessity. Now researchers from Cornell University have developed a new vaccine that acts faster, lasts longer and fights multiple strains, potentially cutting back the jab from once a year to once a decade.
The humble influenza virus can be quite deadly, particularly to the elderly, so developing a vaccine that protects against multiple or all strains is a priority. Previous work has looked deeper into how the immune system identifies pathogens, discovered more effective antibody candidates, and found a potential way to bolster the “border protection” in the nose.
Every year, the World Health Organization releases a list of the flu strains that will most likely be doing the rounds that season, and leaves it to pharmaceutical companies to develop vaccines that target this most-wanted list. But it’s a gamble: sometimes, it’s the unexpected strains that take off, rendering many flu shots ineffective that year.
“Epidemiologists monitor what strains of influenza are circulating in Southeast Asia,” says David Putnam, co-author of the new study. “They usually choose three or four of them, and they predict what the prevailing circulating strains will be. Usually they’re right, but sometimes they’re wrong, and it changes every year because proteins in the virus mutate.”
Proteins on the surface of the virus are the ones most likely to mutate, while those deeper inside the cell don’t change as often or as drastically. Targeting these inner proteins should therefore make for a more effective drug, and that’s exactly the mechanism behind a universal flu vaccine that’s set to start human trials in the UK this (northern) winter.
The Cornell-developed drug works the same way. The target is Matrix-2 (M2), an unchanging protein that’s found naturally in strains of human, bird and swine flu. The researchers took two genetic sequences of bird flu, one from pigs and one from humans, all of which contain M2, and combined them all into one drug.
This antigen is then loaded into a bacterial outer membrane vesicle (OMV), a nanostructure engineered from a safe strain of E. coli, to create a vaccine that should start acting faster, last longer, and fight multiple strains of the flu.
“So even if, say, the human strain mutates, we know where it came from and it’s going to look like the other two,” says Putnam. “We kind of covered all the bases.”
The team tested the vaccine on mice, and found that antibody numbers rose in four weeks, about half the time it took for a control group that received a two-shot prime/boost vaccine. To test how long that protection lasted, the team then gave the mice a lethal dose of influenza A six months after the shot, and 100 percent of them survived.
Six months is about a quarter of a mouse’s lifespan, so the researchers believe that when scaled up for humans, this vaccine could remove the need for yearly flu shots.
“Even if we have to give a booster shot every 10 years, like tetanus, that’s still very good,” says Putnam. “Theoretically it should last a long time.”
As an added bonus, the delivery method makes the drug less expensive to produce. Vaccines are normally bolstered by a substance called an adjuvant, which improves the body’s immune response. But in this case, that role is fulfilled by the OMV, which still contains signals of the E. coli it was made from.