Nebraska Scientists Closer to Universal Swine Flu Vaccine: Long-Term Live Pig Experiment Shows Promising Results

A successful long-term experiment with live pigs indicates that Nebraska scientists may be one step closer to achieving a safe, long-lasting, and potentially universal vaccine against swine flu.

The results are not only important for the swine industry, but have significant implications for human health. This is because pigs act as “mixing vessels” where various strains of swine and avian influenza can reconfigure and become transmissible to humans.

In fact, the 2009 swine flu pandemicwhich involved a variant of the H1N1 strain, first emerged in pigs before infecting about a quarter of the world’s population in its first year, causing nearly 12,500 deaths in the United States and perhaps as many as 575,000 worldwide, according to the Centers for Disease Control and Prevention.

“Given the important role that pigs play in the evolution and transmission of potential pandemic strains of influenza and the substantial economic impact of swine influenza viruses, it is imperative that efforts be made to develop more effective vaccination strategies in populations. of vulnerable pigs,” says Erika Petro-TurnquistPhD student and lead author of the study recently published in Frontiers in Immunology.

Petro-Turnquist is advised by Eric Weaver, associate professor and director of the Nebraska Virology Center. Weaver’s lab is spearheading an effort that uses Epigraph, a data-driven computing technique co-developed by Bette Korber and James Theiler from Los Alamos National Laboratory, to create a broader vaccine against influenza, which is notoriously difficult to prevent because it mutates rapidly.

Currently, pork producers attempt to control swine flu by using commercially available vaccines derived from whole inactivated viruses and weakened live viruses. As of 2008, about half of the vaccines in use in the United States were tailored for specific herds, a costly, time-consuming, and ineffective strategy given the rapid evolution of swine flu.

The epigraph algorithm allows scientists to analyze countless amino acid sequences among hundreds of influenza virus variants to create a vaccine “cocktail” of the three most common epitopes: The viral protein fragments that trigger the immune system response. It could be a path toward a universal flu vaccine, which the National Institutes of Health defines as a vaccine that is at least 75% effective, protects against multiple types of flu viruses for at least one year, and is adequate for all age groups.

“The first epitope looks like a normal flu vaccine gene, the second looks a little weird, and the third is rarer,” Weaver says. “We’re reversing evolution and putting back together these sequences that the immune system recognizes as pathogens. We’re relinking them computationally, and that’s where the power of this vaccine comes from, which gives such good protection against such a wide range of viruses.”

In another strategy to increase effectiveness, the vaccine is delivered via adenovirus, a common virus that causes cold-like symptoms. Its use as a vector triggers an additional immune response by mimicking a natural viral infection.

Two years ago, Weaver’s team published the initial results in the magazine Nature Communications, based on tests in mice and pigs. Those findings indicated that the Epigraph-developed vaccine produced immune response signatures and physiological protection against a much broader variety of strains than a widely used commercial vaccine and wild-type influenza strains.

INVESTIGATION

The follow-up study is apparently the first longitudinal study to compare the onset and duration of an adenovirus-vectored vaccine with that of a whole inactivated virus vaccine. The researchers observed 15 female pigs over a period of about six months, the typical life span of a market pig.

One group of five received the Epigraph vaccine, a second group of five received a commercial inactivated whole virus vaccine, and a third group of five received saline to serve as a control group. The pigs received their initial vaccination at three weeks of age and a booster injection three weeks later. Their antibody levels and T cell responses were measured weekly for the first month and every 30 days thereafter. At six months of age, they were exposed to a different strain of swine flu than those directly represented in the vaccine.

Los pigs given the Epigraph vaccine showed more rapid and long-lasting antibody and T-cell responses to vaccines. After exposure to the swine flu virus, Epigraph-vaccinated pigs showed significantly better protection against the disease: less viral shedding, fewer symptoms of infection, and stronger immune system responses.

“Those pigs were about five pounds when we vaccinated them and at the end of the study, six months later, they were over 400 pounds,” Weaver says. “It’s amazing that this vaccine stayed above that growth rate. It continues to expand as the animal grows.”

Weaver’s team is continuing the research, and next steps include larger studies and possibly a commercial partnership to bring the vaccine to market.

“The more times we do these studies, the more confident we can be that this vaccine will be successful in the field,” Weaver says.