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Influenza kills an average of 36,000 Americans annually and hospitalizes another 200,000. Because influenza viruses continuously mutate, vaccines need to be reformulated annually to match the current circulating strains and we all need a new "flu shot" every Fall. A universal influenza vaccine -- one that is effective against multiple strains for several years -- has long been a goal of public health scientists. Such a universal vaccine could have an enormous impact on the control of influenza. If we didn't all need that new flu shot every year to stay protected against the flu, we could expect many of those 36,000 deaths to be prevented.
A number of researchers have identified antibodies that neutralize a broad range of influenza viruses in animal models. These antibodies attach to a region on the stem of hemagglutinin (HA), a protein on the surface of the virus that allows it to enter and spread from cell to cell. Unlike HA's head -- which mutates readily, allowing the virus to become unrecognizable to antibodies -- the stem is less likely to mutate and varies relatively little from strain to strain. Unfortunately, researchers haven’t been able to generate these broadly neutralizing antibodies by vaccination.
Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), led by Dr. Gary J. Nabel, may now be getting closer to the development of a universal flu vaccine. Their research was aimed at developing a vaccine to elicit antibodies to multiple strains of H1N1, which include the virus responsible for last year's flu pandemic. In parallel experiments with mice, ferrets and monkeys, these researchers first primed the animals’ immune systems using a vaccine made from a piece of DNA derived from a 1999 circulating flu virus. The mice and ferrets then received a booster dose of another virus -- either the 2006-2007 seasonal flu vaccine or a vaccine made from a weakened cold virus containing HA. Monkeys were boosted with the seasonal flu vaccine only. The researchers found that animals given the prime/boost vaccination produced antibodies capable of neutralizing numerous H1N1 strains -- ranging from a highly virulent one that emerged in 1934 to others that appeared in 2006 and 2007. Although the vaccines were made from H1 subtypes, the antibodies neutralized other subtypes as well, including H5N1 (avian influenza). The broadly neutralizing antibodies, as expected, recognized the HA stem.
The NIAID researchers measured how well the vaccination protected animals from infection. Three weeks after receiving the boost, mice were exposed to high levels of the deadly 1934 flu virus, and 80% survived. Mice receiving DNA only, seasonal flu vaccine only, or a placebo all died. Trials to assess safety and immune responses to such a prime/boost influenza vaccine are already under way in humans. "We may be able to begin efficacy trials of a broadly protective flu vaccine in 3 to 5 years," predicts Dr. Nabel.
