Flu viruses are constantly mutating and every year the seasonal flu shot is updated to keep up with the viruses that are making people sick. Readers interested in the prospect of a â€œuniversal flu vaccineâ€ may have noticed some experimental progress on that theme this week.
Some background: the head region of the flu virusâ€™s mushroom-like hemagglutinin protein is more variable, and more exposed to the immune system, while the stem/stalk region is less variable.
The underlying idea is: if someoneâ€™s immune system is exposed to flu viruses different enough than what it has seen before (like in the 2009 H1N1 outbreak and the H5N1 study), the antibodies to the stem region become more important and more prominent.
The NIAID team fused the flu hemagglutinin to ferritin, a platform for further protein engineering.
This week, what the researchers from NIAID (Nature Medicine) and Scripps/J&J (Science) showed is that experimental vaccines made from the stem region only can be broadly protective in several animal models. This required some protein engineering and reconstruction because chopping off the head of the hemagglutinin protein makes it fall apart.
It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After divertingÂ some of these topics into the 2015 crystal ball,Â I corralledÂ them into themes.
Vaccine researchers have developed a strategy aimed at generating broadly cross-reactive antibodies against the influenza virus: embrace the unfamiliar.
In recent years, researchers interested in a “universal flu vaccine” identified a region of the viral hemagglutinin protein called the stem or stalk, which doesn’t mutate and change as much as other regions and could be the basis for a vaccine that is protective against a variety of flu strains.
In an Emory Vaccine Center study, human volunteers immunized against the avian flu virus H5N1 readily developed antibodies against the stem region of the viral hemagglutinin protein. In contrast, those immunized with standard seasonal trivalent vaccines did not, instead developing most of their antibodies against the more variable head region. H5N1, regarded as a potential pandemic strain, is not currently circulating in the United States and the volunteers had not been exposed to it before.
The results were published Monday, August 25 inÂ PNAS.
The key to having volunteers’ bodies produce antibodies against the stem region seemed to be their immune systems’ unfamiliarity with the H5N1 type of virus, says lead author Ali Ellebedy, PhD, postdoctoral fellow in the laboratory of Rafi Ahmed, PhD, director of Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.
Note: for a counterpoint, check out this 2013 Science Translational Medicine paper on how vaccination that induces anti-stem antibodies contributes toÂ enhanced respiratory disease in pigs.
Immunologists reported recently that the drug rapamycin, normally used to restrain the immune system after organ transplant, has the unexpected ability to broaden the activity of a flu vaccine.
The results, published in Nature Immunology, indicate that rapamycin steers immune cells away from producing antibodies that strongly target a particular flu strain, in favor of those that block a wide variety of strains. The results could help in the effort to develop a universal flu vaccine.
This study was inspired by a 2009 Naturestudy from Koichi Araki and Emory Vaccine Center director Rafi Ahmed, reports Jon Cohen in Science magazine. Read more
Francis Collins, director of the National Institutes of Health, made a splash last week predicting the arrival of a universal flu vaccine in the next five years.
Francis Collins told USA Today he is "guardedly optimistic" about the possibility of long-term vaccination that could replace seasonal flu shots.
His prediction came at the same time as a report in Science identifying an antibody that can protect against several strains of the flu virus.Â Taking a look at the Science paper, how the scientists found the “super antibody” seems remarkably similar to how Emory’s Jens Wrammert, Rafi Ahmed and colleagues found a similar broadly protective antibody.Â Their results were published in the Journal of Experimental Medicine in January.
In both cases, the researchers started with someone who had been infected with the 2009 H1N1 swine origin flu virus, sifted through the antibodies that person produced and found some that reacted against several varieties of the flu virus. There must be something special about that 2009 pandemic strain!
Scientists at Emory and the University of Chicago have discovered that the 2009 H1N1 flu virus provides excellent antibody protection. This may be a milestone discovery in the search for a universal flu vaccine.
Researchers took blood samples from patients infected with the 2009 H1N1 strain and developed antibodies in cell culture. Some of the antibodies were broadly protective and could provide protection from the H1N1 viruses that circulated over the past 10 years in addition to the 1918 pandemic flu virus and even avian influenza or bird flu (H5N1).
The antibodies protected mice from a lethal viral dose, even 60 hours post-infection.
Some of the antibodies stuck to the â€œstalkâ€ region, or hemagglutinin (H in H1N1) protein part of the virus. Because this part of the virus doesnâ€™t change as much as other regions, scientists have proposed to make it the basis for a vaccine that could provide broader protection. The antibodies could guide researchers in designing a vaccine that gives people long-lasting protection against a wide spectrum of flu viruses.
The paperâ€™s first author, Emory School of Medicineâ€™s Jens Wrammert, PhD, says â€œOur data shows that infection with the 2009 pandemic influenza strain could induce broadly protective antibodies that are very rarely seen after seasonal flu infections or flu shots. These findings show that these types of antibodies can be induced in humans, if the immune system has the right stimulation, and suggest that a pan-influenza vaccine might be feasible.”
Last year, when the H1N1 flu epidemic was a major public health concern, a relatively low proportion of individuals getting sick were elderly, compared to previous flu epidemics. To explain this, scientists hypothesized that flu strains that circulated decades ago were similar enough to the novel swine-origin H1N1 strain toÂ provide some immune protection.
A universal flu vaccine would eliminate the guesswork associated with the yearly flu shot
Now, researchers at Emory’s Influenza Pathogenesis & Immunology Research Center have directly tested that hypothesis in mice, and it holds up. Exposure of mice to flu strains that circulated in 1947 or 1934 induced “robust cross-protective immune responses” and can protect them against a lethal challenge with 2009 H1N1 virus, they report in Journal of Immunology.
Ioanna Skountzou and Dimitrios Koutsananos are co-first authors of the paper.
The Emory team, led by Joshy Jacob, also reports that antibodies produced in response to the 2009 H1N1 flu strain exhibit broad cross-reactivity — they react with other H1N1 strains as well as against H3N2 flu strains. They write:
The fact that the 2009 H1N1 virus can induce such cross-reactive Abs raises the intriguing possibility that viruses such as A/California/04/2009 can be used for vaccines to induce broadly cross-reactive humoral immune responses against influenza viruses. Identifying the mechanism behind this broad reactivity may enable us to design broadly cross-reactive universal influenza vaccines.
National Institute of Allergy and Infectious Diseases director Tony Fauci, when he was at Emory for the H1N1 flu conference in April, discussed the idea of a universal flu vaccine: