# 5121
World War I was brought to a halt, in part, due to the massive wave of pandemic influenza that – by November of 1918 - had crippled the ability of soldiers and sailors to fight on both sides of the conflict.
Nearly 25 years later, when WWII broke out, concerns arose that once again putting hundreds of thousands of troops in close quarters might spark another global influenza epidemic (it didn’t).
This time, a decade after the influenza virus had finally been isolated, scientists had a new, experimental vaccine that – starting in 1943 -was widely used on servicemen.
This first vaccine was reportedly effective during the 1943-44 and the 1944-45 flu seasons, but suffered an almost complete failure during the 1946-47 season (see doi: 10.1073/pnas.162366899) when the predominate influenza strain shifted sharply antigenically.
First detected on US military bases in Japan in 1946, this new virus spread quickly around the world, but is little remembered today because it produced few excess deaths.
What this did demonstrate was that to be effective, influenza vaccines have to be updated each year to keep up with the rapidly evolving influenza virus.
More than sixty years later, scientists are still scrambling to stay one-step ahead of the multiple strains of influenza in circulation, by trying to guess what strains will be infecting people more than 6 months in advance.
Some years, they get it right. Some years . . . well, it isn’t easy when nature’s lab is open and experimenting 24/7.
The Holy Grail for flu vaccine researchers is a universal vaccine – one that would protect against multiple (even antigenically shifted/drifted) strains and that would remain protective for many years.
This would solve two huge problems.
First, it would end (or at least greatly reduce) the constant game of playing catch-up with evolving and mutating viruses.
And second, if a shot could be good for 5 or more years, you could vaccinate a much larger portion of the world’s population over time.
We could conceivably stop the next global pandemic in its tracks, by already having `herd immunity’.
We aren’t there, of course. But the NIH, and many other researcher entities are hard at work on finding the breakthrough that will make this a reality.
A few past blogs on this hunt, include:
Towards A Universal Flu Vaccine
NIH: Progress Towards A Universal Flu Vaccine
Uncovering Influenza's Achilles Heel
This week Anthony S. Fauci, M.D., NIAID director, and Gary J. Nabel, M.D., Ph.D., director of the NIAID Vaccine Research Center, have published a commentary on the prospects for a universal vaccine in Nature Medicine.
GJ Nabel and AS Fauci. Induction of unnatural immunity: Prospects for a broadly protective universal influenza vaccine. Nature Medicine DOI: nm.2272 (2010).
While this is (alas) behind a pay wall, we can get a pretty fair idea of the contents from this NIH press release.
NIH Scientists Consider Prospects for a Universal Influenza Vaccine
WHAT:
The costly, time-consuming process of making, distributing and administering millions of seasonal flu vaccines would become obsolete if researchers could design a vaccine that confers decades-long protection from any flu virus strain. Making such a universal influenza vaccine is feasible but licensing it may require innovation on several fronts, including finding new ways to evaluate the efficacy of vaccine candidates in clinical trials, conclude scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
In a Nature Medicine commentary, authors Anthony S. Fauci, M.D., NIAID director, and Gary J. Nabel, M.D., Ph.D., director of the NIAID Vaccine Research Center, contrast the envisioned universal influenza vaccine with today’s seasonal influenza vaccines. Current seasonal flu vaccines prompt immune responses that mimic those made following natural exposure to the flu virus. Both exposure and vaccination elicit antibodies directed at the roundish head portion of a lollypop-shaped flu protein called hemagglutinin (HA). But the composition of HA’s head changes from year to year, gradually becoming unrecognizable to previously made antibodies. Thus, vaccination—which induces antibodies tailored to that year’s HA head region—must be repeated annually to maintain immunity to the virus.
A universal flu vaccine would have to elicit a type of immune response that rarely occurs naturally, note Drs. Fauci and Nabel. A detailed understanding of flu virus structure may make such a vaccine possible, they add. For example, scientists have identified a region of HA’s stem that is shared among diverse strains, and a research group at NIAID’s Vaccine Research Center recently created influenza vaccines that elicit antibodies aimed at this shared region, rather than at the quick-changing head. Animals that received the experimental vaccines were protected from a diverse array of flu virus strains.
In essence, say the authors, thanks to the growing body of knowledge about flu viruses and their interactions with the cells of humans and animals they infect, it may one day be possible to make a universal flu vaccine that improves on nature. They also outline how such a vaccine might proceed through stages of clinical testing and on toward licensing. For example, they sort the 16 known influenza virus subtypes into three tiers based on their likelihood of causing widespread disease in humans. Drs. Fauci and Nabel suggest that vaccine development might be prioritized to produce first-generation universal influenza vaccine candidates that protect against multiple virus strains within the highest priority group.
For more information about NIAID research on influenza, visit the NIAID flu Web portal.
