July 18, 2010 — A universal influenza vaccine tested on mice and ferrets successfully immunized the animals against a virus strain from 1934, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID).
The experimental vaccine, which consisted of a primer dose and a booster, generated antibodies in mice and ferrets against virus strains from 4 different decades — not only H1 subtypes of influenza virus A but also other subtypes such as H5N1, or avian influenza.
The research, led by NIAID scientist Gary Nabel, MD, PhD, appeared online July 15 in Science. The team also included scientists from the US Centers for Disease Control and Prevention and a private research company.
The animal study, which also included monkeys, comes at a time when scientists are conducting human trials of "prime-boost" influenza vaccines to test their safety and ability to trigger an immune response.
"We may be able to begin efficacy trials of a broadly protective flu vaccine in 3 to 5 years," Dr. Nabel said in a press release issued yesterday by the National Institutes of Health. He added that the research published in Science could help scientists select candidate vaccines for large-scale human studies.
In contrast to the experimental vaccine in the NIAID study, current influenza vaccines do not produce such broadly neutralizing antibodies and so must be reformulated each year to match the predominant virus strains in circulation.
The prime-boost combination could eliminate the need for annual influenza shots, said Dr. Nabel. Instead, influenza vaccination could resemble how people are inoculated against diseases such as hepatitis, "where we vaccinate early in life and then boost immunity through occasional, additional inoculations in adulthood."
Peculiarity of HA Surface Protein Key to Vaccine's Promising Results
Dr. Nabel and his team first primed the animals' immune systems with a vaccine made from DNA that encodes the hemagglutinin (HA) surface protein, a mushroom-shaped structure, from a 1999 H1N1 influenza strain appearing in the 2006 to 2007 seasonal vaccine. Mice and ferrets then received a booster dose of either the seasonal vaccine for 2006-2007 or one made from a weakened adenovirus that expresses the HA surface protein. The only booster shot for monkeys was the seasonal influenza vaccine.
The anatomy of the HA surface protein, which supplies the "H" in the nomenclature of virus strains such as H1N1, is key to the experimental vaccine's promising results (the "N" comes from the protein neuraminidase). The combination of a primer and booster triggered an immune response to the stem of the HA surface protein, as opposed to its head. Although the head of the protein mutates easily, thwarting the ability of antibodies to recognize the virus, the stem is largely the same from strain to strain.
In principle, said Dr. Nabel, antibodies generated against the stable stem of the HA surface protein should neutralize multiple strains of influenza. The results of the study supported his hypothesis. All the animals that had received the prime/boost vaccine produced antibodies against virus strains from 1986, 1995, 1999, and 2007. Mice and ferrets generated antibodies against strains from additional years, including 1934.
The ability of the prime-boost vaccine to elicit a wide range of antibodies is promising, but Dr. Nabel's team also wanted to know how well the vaccine would guard animals from influenza. So they exposed 20 mice to lethal levels of the 1934 virus 3 weeks after a booster dose was administered. Eighty percent of the mice survived. In contrast, all mice that received only the primer, only the seasonal flu vaccine, or a sham prime-boost combination died.
Similar results were achieved in challenge tests with ferrets using the 2 kinds of boosters after the primer. All 4 ferrets that received the seasonal influenza vaccine as a booster achieved protection from a 2007 virus strain, and all 6 ferrets receiving the adenovirus booster were likewise protected from the 1934 strain. The researchers noted that ferrets provide a good animal model for predicting how well influenza vaccines will work in humans.
Science. Published online July 15, 2010.
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Authors and Disclosures
Journalist
Robert Lowes
Freelance writer, St. Louis, Missouri
Disclosure: Robert L. Lowes has disclosed no relevant financial relationships.
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