The flu shot stimulates immunity against a protein called hemagglutinin, which extends from the surface of the flu virus. Hemagglutinin (shown here as little spikes) has a "head" and a "stem."
Credit: Kateryna Kon/Shutterstock
A new type of flu vaccine that contains "ancestral" flu virus genes shows promise in providing broad protection against many different strains of the flu, according to an early study in animals.
When researchers gave this new vaccine to mice, it protected up to 100 percent of the animals, meaning they survived after being given typically lethal doses of nine different flu viruses. Mice that were given high doses of the vaccine didn't even get sick from the typically lethal doses of flu, the researchers said.
In contrast, all of the mice that were given traditional flu shots got sick and died when exposed to the same lethal doses of flu.
Because the study was conducted in mice, it's too soon to say whether the vaccine would successfully work in humans. [6 Myths About the Flu Vaccine]
But the researchers hope that their approach might one day lead to a "universal" flu vaccine that would provide long-term protection against flu viruses. "The ultimate goal is to be able to vaccinate once and provide lifelong protection," lead study author Eric Weaver, an assistant professor at the University of Nebraska-Lincoln, said in a statement.
Because flu viruses mutate rapidly, researchers have found it difficult to develop a flu vaccine with long-term protection. Currently, researchers develop a new seasonal flu vaccine every year based on which flu strains they predict will be circulating in the fall and winter.
The seasonal flu shot contains weakened or dead versions of flu viruses. The shot stimulates immunity against a protein called hemagglutinin, which extends from the surface of the flu virus. (This protein consists of a "head" and a "stem," and flu shots generally stimulate immunity against the head of the hemagglutinin protein.)
A number of researchers are investigating different strategies to make a universal flu shot, including developing vaccines that target the "stem" of the hemagglutinin protein (which tends to change less from season to season) rather than the head.
But in the new study, the researchers took a different approach. Their vaccine contains "ancestral" or "consensus" flu genes from the four major flu strain types: H1, H2, H3 and H5. These are genes that represent common or ancestral sequences shared by many different flu viruses.
To deliver these genes to the mice in the study, the researchers used an adenovirus, which causes the common cold, that had been altered so it was harmless and could carry the four ancestral genes.
After vaccinating the mice, the researchers infected them with nine strains of the flu — including strains of H1N1, H3N1, H3N2 and H5N1— at a dose that typically kills mice. But 100 percent of the vaccinated mice survived infection with seven out of the nine flu viruses given at typically lethal doses, the study found.
However, future studies in animals will be needed to better determine the safety and efficacy of the vaccine
An artist's rendition of HIV (foreground). The knobs (purple) covering the virus are sugar-protein molecules, including gp120, that shield the rest of the virus (pink).
Credit: National Cancer Institute
Researchers at the University of Maryland and Duke University have designed a novel protein-sugar vaccine candidate that, in an animal model, stimulated an immune response against sugars that form a protective shield around HIV. The molecule could one day become part of a successful HIV vaccine.
"An obstacle to creating an effective HIV vaccine is the difficulty of getting the immune system to generate antibodies against the sugar shield of multiple HIV strains," said Lai-Xi Wang, a professor of chemistry and biochemistry at UMD. "Our method addresses this problem by designing a vaccine component that mimics a protein-sugar part of this shield."
Wang and collaborators designed a vaccine candidate using an HIV protein fragment linked to a sugar group. When injected into rabbits, the vaccine candidate stimulated antibody responses against the sugar shield in four different HIV strains. The results were published in the journal Cell Chemical Biology on October 26, 2017.
The protein fragment of the vaccine candidate comes from gp120, a protein that covers HIV like a protective envelope. A sugar shield covers the gp120 envelope, bolstering HIV's defenses. The rare HIV-infected individuals who can keep the virus at bay without medication typically have antibodies that attack gp120.
Researchers have tried to create an HIV vaccine targeting gp120, but had little success for two reasons. First, the sugar shield on HIV resembles sugars found in the human body and therefore does not stimulate a strong immune response. Second, more than 60 strains of HIV exist and the virus mutates frequently. As a result, antibodies against gp120 from one HIV strain will not protect against other strains or a mutant strain.
To overcome these challenges, Wang and his collaborators focused on a small fragment of gp120 protein that is common among HIV strains. The researchers used a synthetic chemistry method they previously developed to combine the gp120 fragment with a sugar molecule, also shared among HIV strains, to mimic the sugar shield on the HIV envelope.
Next, the researchers injected the protein-sugar vaccine candidate into rabbits and found that the rabbits' immune systems produced antibodies that physically bound to gp120 found in four dominant strains of HIV in circulation today. Injecting rabbits with a vaccine candidate that contained the protein fragment without the sugar group resulted in antibodies that primarily bound to gp120 from only one HIV strain.
"This result was significant because producing antibodies that directly target the defensive sugar shield is an important step in developing immunity against the target and therefore the first step in developing a truly effective vaccine," Wang said.
Although the rabbits' antibodies bound to gp120, they did not prevent live HIV from infecting cells. This result did not surprise Wang, who noted that it usually takes humans up to two years to build immunity against HIV and the animal study only lasted two months.
"We have not hit a home run yet," Wang noted. "But the ability of the vaccine candidate to raise substantial antibodies against the sugar shield in only two months is encouraging; other studies took up to four years to achieve similar results. This means that our molecule is a relatively strong inducer of the immune response."
The researchers' next steps will be to conduct longer-term studies in combination with other vaccine candidates, hone in on what areas of gp120 the antibodies are binding to and determine how they can increase the antibodies' effectiveness at neutralizing HIV.
Path of a Pandemic: Map Shows How H1N1 Swine Flu Spread
A new map shows the path of H1N1 "swine flu" as it spread across the United States in the fall of 2009. Above, the map shows how the "fall wave" of H1N1 began in Georgia and Alabama, and radidated outwards across the country. The side plot shows how flu activity peaked at different times in Atlanta and Boston.
Credit: PLOS Computational Biology
A new map shows the path of H1N1 "swine flu" as it spread across the United States in the fall of 2009, when the brunt of the pandemic hit the country.
The map is based on reported visits to the doctor for flulike illness in 271 U.S. cities in the late summer and fall of 2009 (when visits for other respiratory illnesses are typically low).
Although there had been some H1N1 transmission in the spring of that year, the outbreak did not become widespread in the U.S. until the fall, the researchers said. This "fall wave" started in the Southeast — in Alabama and Georgia — and then radiated outward, taking about three months to spread across the entire country. States in the Northeast, such as New York and Massachusetts, were the last to be hit.
Interestingly, the study found that the disease mainly spread over short distances, between areas that were very close to each other.
"It is remarkable that the main 2009 pandemic wave — set in an era of intense air traffic and regional ground transportation — showed such a short-range mode of spread," the researchers wrote in the June 12 issue of the journal PLOS Computational Biology.
One reason for this could be that children were a predominant source of infection, and kids don't usually travel long distances as often as adults do, the researchers said.Another factor that appears to have helped fuel flu transmission was the fact that schools opened in the fall, the researchers said.
"The findings underline the critical role that school-age children play in facilitating the geographic spread of pandemic influenza," the researchers said.
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