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Overcoming the Hurdles to a Universal Flu Vaccine

Researchers are Closing in on a General Approach to Prevent the Flu

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Overcoming the Hurdles to a Universal Flu Vaccine

Yearly Flu Vaccine May Become Thing of the Past

CDC/Judy Schmidt
Updated December 06, 2012

The flu is often not thought so serious but it kills from 3,000 to almost 50,000 individuals per year in the US, depending on the severity of the season. Unfortunately, yearly flu vaccinations appear to do a relatively poor job defending against this seasonal illness. Why is this? The problem is that there are hundreds of strains of influenza virus that continually mutate to produce new variations. There is no general vaccine that protects against all the variations. However, researchers are working on developing one.

Influenza Variations Make Immunity Difficult

The most serious flu virus for humans is influenza type A. This highly variant influenza group is usually the culprit of the seasonal illness and variations of the type A influenza were responsible for all the major flu pandemics of the last century, such as the 1918 Spanish flu, the 1957 Asian flu, and the 1968 Hong Kong flu. Type B influenza can also infect humans with similar symptoms but it is less adaptive and virulent.

Vaccines protect against the flu by mimicking an influenza infection using a severely weakened version of the virus, or even just a part of the virus. The body, in turn, mounts an immune response that produces anti-influenza antibodies which are later ready to attack the real virus should an actual infection occur. However, vaccines can only be produced against a small number of the plethora of influenza virus variations at a time. Each year companies make the seasonal flu vaccine against the top two type A strains and one type B strain predicted to be most prevalent by the Centers for Disease Control (CDC) .

As opposed to the current vaccination approach, however, consistent elements across all flu strains, if they can identified, may be used to engineer a vaccine that enables the body to recognize all variants of influenza. With this approach, one vaccination would produce immunity against all flu variants. This is the elusive goal of a number of research groups.

Zeroing in on Ways to Target All Influenza

Several groups are working to identify common parts of the flu viruses that can be targeted by antibodies. The specific surface structure that an antibody recognizes and binds to is called an epitope. The researchers are looking for epitopes generally common to broad groups of influenza viruses. These epitopes can then be engineered into a vaccine to get patients to produce the antibodies that provide broad immunity to many types of influenza viruses.

A recent blog post on this site noted that researchers at the Scripps Research Institute in San Diego, in collaboration with the Dutch company Crucell, screened flu antibodies from the immune cells of volunteers to find ones that target the three common epitopes on most influenza B viruses. This result followed up previous work by the same lab a year earlier when they found antibodies to two epitopes common to influenza type A viruses. Around that time, another group in Switzerland also identified an antibody that neutralized two subgroups of influenza type A. Also, recently, researchers at Emory found a potentially targetable conserved type A epitope by screening patients exposed to the highly virulent H1N1 influenza.

Results from the studies mentioned above show that it is possible to target whole influenza groups rather than individual strains. It is likely that the difficulty in finding these common viral epitopes previously stemmed from limitations of the screening technology required to analyze hundreds of thousands of antibodies for effectiveness against many different influenza variants. Advances in these screening techniques in the last few year have made this research more tractable.

Companies Already Testing More Effective Engineered Flu Vaccines

As an alternative to screening antibodies from flu-exposed patients, Israeli-based BiondVax Pharmaceuticals analyzed viral structures to identify putative common influenza epitopes, then modeled them using peptides which were then tested for immune responsiveness. From this work, they have produced the Multimeric-001 vaccine which is now in trials. Although it may provide more universal immunity to the flu, the vaccine is being developed as a supplement to boost the effect of the standard seasonal flu vaccine. This approach avoids the need to prove the vaccine elevates antibodies to influenza haemagglutinin proteins, which is the standard way to measure efficacy of a flu vaccine but not the way BiondVax's vaccine works.

Another company, Inovivo, in Pennsylvania, has also adopted the approach of analyzing multiple strains to identify common stable epitopes, but they are looking at variance of the DNA, rather than the proteins as Biovax is doing, to find conserved antigenic features. They have recently started trials in Canada of a vaccine for all influenza A H1N1 sub-types.

Getting Good Immune Responses Even with Prior Vaccinations

One other concern regarding a universal flu vaccine has recently been resolved. Since a vaccine's effectiveness relies on the body's own immune response, there was considerable concern that immunity generated by flu vaccinations would inhibit a strong reaction of a new generally effective universal vaccine. In other words, if someone has already been vaccinated against some forms of the flu, they may not respond strongly to a new vaccine. However, researchers at the NIH Vaccine Research Center have recently shown that this does not seem to be a problem.

A Future without the Flu?

An actual vaccine is still some ways off, but many of the hurdles to developing such a vaccine have been overcome in just the last couple years. Research has finally reached a point where it makes sense to begin medical trial to test formulations. With any luck, a universal flu vaccine may be a reality in just a few more years.

Also, while much of the research cited above may enable engineering of a vaccine that induces injected patients to make universal anti-flu antibodies, the results may also lead to other therapeutics. For example, by using genetically engineered forms of the flu-targeting antibodies, it may be possible to create an anti-flu drug that might be used to prevent infection of high risk health care personnel during an outbreak or to actually treat patient that have come down with the flu.

With any luck, the seasonal flu may become a thing of the past in a few more years. This development should eliminate over 200,000 hospitalizations a year and save countless more from the periodic headache, coughing, fever, and fatigue. Of course, then we will have to make up with a new excuse to take the occasional day off work too.

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