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How Close Is a Universal Influenza Vaccine That Could Provide Lifelong Immunity with One Shot?

The rapidly mutating strains of flu virus have so far thwarted efforts to develop a vaccine that could knock out all varieties with a single injection, but recent advances suggest a synthetic solution. The head of Mount Sinai School of Medicine's microbiology department explains
annual flu shot could be a thing of the past with universal influenza vaccine



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The annual jab fest for the seasonal flu is already underway, scaring needle-wary youngsters and leaving many grown-ups wondering if the annual stick in the arm is right for them.

In recent years research has shown that the mélange of strains in each year's flu shot and exposure to previous flus can provide some immunity decades later to people exposed to closely related influenza iterations. For example, people who were born before the mid-1950s (when H1N1 stopped circulating) showed a better defense against the recent H1N1 virus. But because the virus is so adept at eluding the body's immune system via mutation, many new varieties crop up each year. After its latest battle with H1N1, a U.S. Centers for Disease Control and Prevention committee recommended in February that everyone six months and older get the annual vaccine, a step that should improve immunity against future pandemics as well as seasonal cycles of the flu.

The hunt for a universal flu vaccine, a single shot that would provide lifelong immunity, has been going on for decades, and many teams of researchers have been on the case. The effort is complicated because there are some 16 types of key surface proteins (hemagglutinin) that help the virus bind to host cells, in addition to the several varieties of viral neuraminidase proteins. (These proteins are what the "H" and "N" stand for in viral designations such as H1N1.) Flu vaccines work by introducing a killed version of circulating virus strains, which trains the body's immune system to recognize and attack similar invaders in the future. Changes in the viruses' proteins help it evade identification by the immune system.

A series of discoveries by different groups of researchers have zeroed in on a highly conserved (nonmutated) region of the virus. And a new study, published online October 18 in Proceedings of the National Academy of Sciences, has piggybacked on these findings to develop synthetic vaccine that has been effective in warding off several different types of influenza in mice. How does it work—and could it work in humans?

Scientific American spoke with Peter Palese, a co-author of the new study and chair of the Department of Microbiology at Mount Sinai School of Medicine in New York City, to find out the status of the quest for a universal flu shot.

[An edited transcript of the interview follows.]


So, why do we have to get a flu shot every year?

Some viruses—for example measles, mumps, rubella, poliovirus—do not change over time. Therefore, one vaccination—or one course of vaccinations—may last, if not a whole lifetime, a very long time. The difference with influenza viruses is they undergo a dramatic change every one to five years. The virus is really changing because of what we call antigenic drift and shift.

But this makes it very complex for both vaccine production and administration. Surveillance programs must be used each year—and based on the selection of strains, we usually have three influenza strains in a vaccine each year.

Each year two or sometimes all three of the strains of influenza need to be changed. The need for every annual vaccination is a result of these antigenic changes in the virus each year.

Can some immunity from past shots or exposures protect you against seasonal or epidemic strains, like some older adults who seemed to already have some immunity to H1N1?
The new pandemic H1N1 actually turns out to be related to previous pandemic strains. So the older people are more protected than the younger ones, which is a very unusual situation. One of the few things that get better with old age.

Are we close to being able to develop a universal flu vaccine that would confer immunity against all strains of influenza?
The basis for the new understanding that there might be some universal vaccine possible is that several groups, including ours, identified and isolated monoclonal antibodies. There was some advance in the last one and a half years in that people were able to identify cross-reactive monoclonal antibodies—antibodies that can be protective against a variety of strains. That was not known before, and the reason for the discovery is that the technology has become much better.

We were able to identify what this antibody recognizes. This antibody recognizes this conserved region, which is called a conserved stalk of the virus's hemagglutinin, which is like a mushroom.

The antibodies were against the stalk of this mushroom, and by using this mushroom stalk only, we made synthetic peptides of this stalk. We were able to show in mice that this virus was able to induce a cross-reactive immunoresponse.

The second very exciting thing is that it's a synthetic peptide, which makes it much easier to put into use.

How would this synthetic vaccine be easier to make than the traditional variety, which is grown in chicken eggs?
We would only provide the conserved stalk—or the conserved portion—of the virus's hemagglutinin. And that preparation can be made synthetically by a peptide only about 60 amino acids long. And that, given to a mouse, induces this cross-reactive immunoresponse.

Since flu strains are so good at mutating, is there a chance that they could evolve to get around this sort of vaccine?
The stem—the stalk region—is probably less tolerant to those changes. Never say never, of course, but by virtue of having seen that these regions don't change over 50 or 80 years—of course, I'm exaggerating here, in essence they have not changed—suggests that the virus has not been able to change there. So there is some hope that the virus is not so able to overcome the vaccine.

Right now, worldwide, probably only 5 percent of old people take the influenza vaccine, so it is unlikely that this mutation would happen very fast. So it's a bit like antibiotics: Only if you have excessive use of antibiotics, does resistance become a major problem.

Could a universal vaccine then protect against a pandemic, such as an H1N1 or even H5N1 spread?
They should protect against it. We would provide a herd immunity against every single strain conceivable. It's not 100 percent, but it would certainly dampen any impact a new pandemic strain would have in terms of morbidity and mortality—meaning disease as well as death.

Could these findings be applied to other viruses and vaccines?

Many viruses do not undergo this change, so for those kinds of vaccines there's no need for change because they work very well. There are, however, celebrated cases, such as HIV and hepatitis C, which also undergo a lot of change. The idea of finding conserved domains and using those in vaccines has been around. It just hasn't worked. A similar approach to those two viruses is always possible if one can identify the conserved regions. We can't use a conserved region of the influenza virus to protect against HIV or hepatitis C.

So where is the research now? When might we expect to see a universal flu vaccine?

We only showed it in mice, so one has to extend this to other animal models—the ferret and the guinea pig. And only if those experiments would be successfully completed would we think of going into humans.

It is always much easier to protect mice. You know this from cancer—you can cure cancer in mice, but in humans, it ain't so easy. One has to see if that same approach would also be effective in humans.

We can, for the first time, think about a universal influenza vaccine. Clearly our approach is just the beginning.

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