New Hope! If YOU are one of those sniffling and sneezing with the flu

without having gotten the flu vaccine, or in spite of having gotten it, a universal flu  vaccine is on the horizon.  Not to sound like a Star Wars movie title here, but there is news about a flu vaccine that would be a significant improvement over our existing versions, in being able to adapt to mutations and to cover more strains and variations.

Dodging those shambling sick people, while scrubbing myself with hand sanitizer more or less consistently, I took a moment to wallow instead in indulging my science geek with this article from TheScientist.com, where they are busy "exploring life, inspiring innovation" which sounds a whole lot more fun than snuffling, and sneezing, aching, coughing and complaining. I also have to admit to enjoying an author who finds a way to work in a Tolkein-esque reference to a piece of science writing.

I hope that as you read about the possibilities of this kind of a vaccine method, you will also keep in mind the virus-transmission aspects of both the bio-fluourescent quality in the research beagles that glow in the dark, and the recent post here about Cows having as much as 25% snake DNA, that they possibly acquired through the DNA piggybacking on virus transmission....  I like to enliven every sneeze and sniffle with the maximum potential significance for readers.

Universal Flu Vaccines Charge Ahead

Researchers and biotech companies are bringing a universal flu vaccine closer to reality.

It’s a frustrating fact of life that coming down with influenza one year doesn’t guarantee anyone a flu-free season the next year. Even the flu vaccine doesn’t provide full-proof protection, as it covers only a select few strains of the virus—a selection that’s based on the World Health Organization’s best bet as to which strains around the world will be most prevalent in the coming flu season.

Unfortunately, those predictions are proved wrong about one time out of 20, explained Sarah Gilbert, who leads the Human Influenza Vaccine Programme at the University of Oxford’s Jenner Institute.

However, some researchers are getting closer to creating the ever-elusive universal flu vaccine, which could protect against a number of influenza viruses at once, including pandemic strains. If successful, universal flu vaccines would take the guesswork out of vaccine planning, and only require booster shots every few years.

One antibody to bind them all

Influenza is an RNA virus that uses its hemagglutinin (HA) protein like a key to allow it to enter and infect target host cells. In response to infection, or to a typical flu vaccine, the body produces antibodies that bind the head of the HA molecule, preventing free-floating virus from entering and infecting cells. However, the head is also the part of the HA protein that the virus most frequently changes via mutation, making the antibodies produced against one strain ineffective against another.

The answer to creating a vaccine that protects against many strains lies in forcing the immune system to make antibodies against the portions of the HA molecule that are shared, or genetically conserved, among most influenza viruses, thus creating a more universal vaccine. But, for unknown reasons, most vaccines don’t elicit such antibodies. So researchers are now trying new ways of enticing the immune system into making antibodies that recognize these general targets and neutralize many types of influenza at once.

“Up until about 4 years ago, we didn’t know much about human broadly neutralizing antibodies,” said Ian Wilson, a structural biologist at The Scripps Research Institute. But the last few years, researchers have found individuals who produce  antibodies that neutralize a wide variety of both influenza A and B strains, showing that “a universal vaccine is possible if you can elicit the same types of antibodies” in others, said Wilson.

Wilson’s lab helped solve the structure of some of these broadly neutralizing antibodies and the region of HA they target—the conserved stem of HA. More recently, Wilson and his collaborators have shown that because HA’s head region has tiny conserved areas, occasionally even an antibody directed at the HA head can have some cross-reactivity among influenza types.

But most researchers think a stronger antibody can be made against regions in the HA stem. Specifically, some researchers think that a “headless” HA proteins could focus the antibody response on the conserved stem region. Others are looking to design vaccines that contain only small portions of the most important conserved segments of the stem region. Still others  are focused on understanding the basic immunology of how antibodies bind and recognize their targets in order to improve vaccines from a different angle, and possibly understand why antibodies aren’t often naturally made to the stalk region, said Wilson.

Several biotech companies are preparing what they hope will become the first universal flu vaccines on the market, though none have been tested as a universal vaccine yet. Most have been tested for safety and ability to stimulate an immune response in healthy volunteers, or boost efficacy of current vaccines with mostly positive results. One strategy being tested combines several conserved regions of flu proteins into one molecule to produce a vaccine that hopefully stimulates an antibody response against a wide variety of strains. This includes the M-001 vaccine from Israel-based BiondVax, which contains regions from HA and two internal virus proteins. When M-001 was combined with the seasonal vaccine, it enhanced immunity to the strains contained in the seasonal vaccine. Other companies are pursuing similar methods, said Gilbert. “They’re all trying to use only very small [conserved] regions, and they all have their own strategies to identify which regions” are the best, as well as ways to produce stronger immune responses, she said.

Delivery service

Changing how vaccines are delivered also has the potential to produce more broadly cross neutralizing antibodies. Last year, researchers at the NIH elicited antibodies against the conserved HA stem region by presenting bird flu HA in two different forms. First they primed with a DNA vaccine—a segment of DNA encoding the HA protein, which host cells produce and present to immune cells—and followed this with a protein-based inactivated H5N1 boost. Using this prime-boost method produced neutralizing antibodies targeting the conserved stem region of HA. 

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