Anatomy of influenza virus. An array of subtypes for the surface coat protein hemagglutinin (blue) is what NIAID scientists used to create their universal vaccine. [CDC/Dan Higgins]
Anatomy of influenza virus. An array of subtypes for the surface coat protein hemagglutinin (blue) is what NIAID scientists used to create their universal vaccine. [CDC/Dan Higgins]

While many of us are spending the last half of the summer deciding where the nicest beaches are and who makes the best island cocktails, infectious disease scientists are looking ahead toward the next inevitable outbreak of the flu. Influenza hunters travel to hot zones that have long been the traditional breeding grounds and launching points for global seasonal pandemics. This is an important part of creating seasonal flu vaccines, which protect against only a few specific strains that researchers predict will be the most common for the upcoming year.

What if we could create a vaccine that could protect against most or all influenza strains? This has been the “grail quest” that numerous infectious disease researchers have strived toward for decades. Now, investigators from the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health, have developed a universal vaccine that may provide broad protection against numerous influenza strains, including ones that could cause future pandemics.   

“The reason researchers change the vaccine every year is that they want to specifically match the vaccine to the particular viruses that are circulating, such as H1N1. If the vaccine is just a little bit different to the target virus, it is not expected to offer much protection,” explained senior author Jeffery Taubenberger, M.D., Ph.D., chief of the Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases at NIAID. “What we have done is design a strategy where you don't have to think about matching the vaccine antigen to the virus at all.”

The findings from this study were published recently in mBio through an article entitled “An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple Subtypes of Influenza A Virus.”

Previous research into universal flu vaccines has focused on finding invariable regions of viral coat proteins that could be exploited to generate an immune response that provides significant protection. However, in this study the scientists took a different approach and engineered a virus-like particle (VLP) that expressed an array of hemagglutinin subtypes from the surface of the influenza virus, including H1, H3, H5, and H7.

“There are 16 different hemagglutinin subtypes that circulate in birds and are thought to be the basis for current and future influenza pandemics,” stated Dr. Taubenberger. “The hypothesis was that the presentation of these different viral proteins would stimulate the development of cross-protective immunity that would provide broader protection against multiple subtypes.”

The H1 and H3 subtypes were chosen as they have been linked to major influenza outbreaks since the 1918 Spanish flu pandemic, which has been estimated to have killed close to 100 million people. The investigators chose H5 and H7 subtypes, as they have been the cause of recent bird flu outbreaks and have a high potential to spread into humans.

The results from the study showed that 95% of mice vaccinated with the novel cocktail were protected against a lethal challenge from eight different influenza strains, while only 5% of unvaccinated mice survived. 

“Almost all of the animals that were vaccinated survived, including mice that were challenged with viruses that expressed hemagglutinin subtypes that were not in the vaccine at all, viruses that expressed H2, H6, H10, and H11,” noted Dr. Taubenberger. “What that suggests is that this approach really gives us broad spectrum protection, and could serve as a basis for an effective pre-pandemic vaccine.”

The NIAID team was also able to show that vaccine’s efficacy lasted for at least 6 months and that it worked well in older mice—an important point since current vaccines are less effective in the elderly.

“These initial findings are very positive and suggest a promising and practical strategy for developing a vaccine with amazing, broad protection,” concluded Dr. Taubenberger.

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