Universal Vaccine

The influenza vaccine, also known as a flu shot, is an annual vaccine to protect against the highly variable influenza virus. An influenza epidemic emerges during flu season each winter. There are two flu seasons annually, corresponding to the occurrence of winter in opposite months in the Northern and Southern Hemispheres. Princeton University-based researchers have found that the universal vaccine could for the first time allow for the effective, wide-scale prevention of flu by limiting the influenza virus' ability to spread and mutate. Universal, or cross-protective, vaccines — so named for their effectiveness against several flu strains — are being developed in various labs worldwide and some are already in clinical trials.

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The researchers recently reported in the Proceedings of the National Academy of Sciences that the new vaccines would make a bout with influenza less severe, making it more difficult for the virus to spread. At the same time, the vaccines would target relatively unchanging parts of the virus and hamper the virus' notorious ability to evolve and evade immunity.

A computational model the team developed showed that these factors could achieve unprecedented control of the flu virus both seasonally and during outbreaks of highly contagious new strains. Cross-protective vaccines could even improve the effectiveness of current vaccines, which are designed to only fight specific flu strains, the researchers report.

"Because the flu quickly evolves to escape host immunity, current vaccines tend to be prioritized for inoculating specific high-risk groups such as asthma sufferers and the elderly every year," Arinaminpathy (one of the authors) said.

The research presents a realistic and important assessment of how the universal vaccines' ability to work against a breadth of flu strains can be wielded to benefit public health, said James Lloyd-Smith, an assistant professor of ecology and evolutionary biology at the University of California-Los Angeles.

"This is the first study that looks at the population consequences of the next generation of vaccines, both in terms of epidemiological impact and evolutionary impact on the virus," Lloyd-Smith said.

Current flu vaccines are produced to counter the influenza strains that the World Health Organization predicts will dominate a particular flu season. Inoculation typically focuses on protecting people who are vulnerable to the virus. However, this approach does not provide long-term or widespread immunity, Arinaminpathy said. The flu virus is always evolving, and so vaccines need to be updated each year.

The reason is that these vaccines zero in on hemagglutinin (HA), proteins protruding from the virus' surface that allow it to attach to and invade host cells. Small mutations in these highly adaptive appendages can create new versions of the virus that often are invulnerable to the vaccine designed for their former selves, a tactic known as immune escape.

Universal vaccines instead bypass the protruding HA surface to target more constant proteins with less evolutionary flair, Arinaminpathy said. Because HAs are still active, the virus may still infect people, but it cannot wreak the same havoc.

A flu pandemic — the sudden and rapid spread of a new, highly contagious strain — is difficult to predict and typically impossible to control through vaccination alone, Arinaminpathy said. But universal vaccines act on virus targets that are relatively constant across all types of flu, even pandemic flu. The researchers found that the vaccines could be deployed on a large scale to avert a pandemic altogether, even if only a proportion of the population received vaccination. The vaccine would raise "herd immunity," wherein even unvaccinated individuals are protected because many people around them are immune.

The research showed that mass immunization with universal vaccines, maintained over several years, would slow viral evolution, or immune escape. Significantly, the researchers found that universal vaccines need not be fully protective to control flu, Arinaminpathy said. To account for any potential differences universal vaccines might have in the level of flu immunity they provide, Arinaminpathy and his colleagues assumed their hypothetical vaccine would not prevent infection, but only reduce the severity of symptoms such as coughing and sneezing, which would bring down the chances of transmitting the virus.

The researchers' simulation showed that overall this led to fewer people becoming infected and, thus, fewer people gaining immunity to the dominant flu strain. That would remove the advantage that any new strains might have, Arinaminpathy said. At the same time, lower rates of infection would mean that fewer people could harbor mutant viruses in the first place because they never caught the original strain.

"Flu control has been dogged by this problem that the virus just keeps evolving. It stays one step ahead of the traditional means of controlling it. So, with strain-specific vaccines, you're always chasing last year's virus," Lloyd-Smith said.

"By using the two vaccines in conjunction, we could get more mileage out of the strain-specific vaccines before they have to be changed," he said. "That gives us an edge in the ongoing evolutionary arms race that we're engaged in with influenza. Universal vaccines won't get rid of the flu completely, but they should take our control efforts to the next level."

Many groups world wide are working on a universal flu vaccine that will not need changing each year, as the sector has been viewed as "increasingly hot". Companies pursuing the vaccine as of 2009 and 2010 include BiondVax, Theraclone, Dynavax Technologies Corporation, VaxInnate, Crucell NV, Inovio Pharmaceuticals,and Immune Targeting Systems. Some universal flu vaccines have started early stage clinical trials.

For further information and photo: http://www.princeton.edu/main/news/archive/S33/01/19A05/index.xml?section=topstories,featured