Two Lawrence Livermore National Laboratory researchers who have worked more than eight years to develop a vaccine for tularemia – also known as rabbit fever – are now part of multi-institutional team to complete its development.

The potential vaccine developed by LLNL contains antigens from the bacteria that causes rabbit fever, a disease that mainly affects rodents, rabbits and domestic mammals, but can also affect humans. Tularemia can cause fever, ulcerations, swelling of the lymph glands, and pneumonia, and is considered a potential bioweapon for terrorists.

Funded by a five-year, $7.5 million grant from the Defense Threat Reduction Agency, LLNL biomedical scientists Nick Fischer and Amy Rasley will collaborate with scientists from the University of New Mexico and the Tulane National Primate Research Center.

“We had confidence that we could develop a tularemia vaccine that would work,” said Fischer, “but it took eight years of hard work and multiple failures to get us where we are today.”

The three-institution development project will be led by Terry Wu, a tularemia expert at the University of New Mexico. He said the project is the result of almost 20 years of research funded by DTRA and the National Institute of Allergy and Infectious Disease.

The scientists will build on a nanotechnology — called nanolipoprotein particles (NPL) — that was developed at LLNL for delivering vaccines and drugs inside the human body. NLPs are water-soluble molecules, as small as 30 billionths of a meter, that resemble the high-density lipoproteins (HDL) that remove fats and cholesterol from cells. LLNL has been working on NPL technology, also known as nanodisc, since 2005.

Using the NLPs as a delivery platform, Lawrence Livermore and the University of New Mexico have identified the proper combination of bacteria antigen and adjuvant to stimulate the body’s immune response. Fischer said the formulation was able to protect against aerosolized tularemia at levels far beyond what was expected.

Although there have been successful efforts to develop tularemia vaccines using live, attenuated strains of the bacteria, the risks are greater than using a “subunit” vaccine using specific proteins instead of the live bacteria.

“The profile for subunit vaccines is significantly safer than for using live, attenuated strains,” Rasley said. “But the tradeoff for that safety is often a less effective vaccine. Our focus has been to enhance the efficacy of the subunit vaccine by inducing a protective immune response. This is where the NLP platform was instrumental in the development of our subunit vaccine because it serves as a delivery tool for the antigens.”

Lab researchers see the NLPs platform as a flexible tool that could be applied broadly to develop vaccines for different pathogens. In October 2019, LLNL announced that the National Institutes of Health had established a cooperative research center at Livermore under a five-year, $10.1 million grant to develop vaccines for chlamydia.

The goals of the tularemia project are to validate the preliminary data, test the vaccine’s ability to protect in more rigorous models, and to optimize production and scale-up of the vaccine formulation.

In addition to Fischer and Rasley, other LLNL biomedical scientists who are part of the team working to developing a tularemia vaccine are Sean Gilmore and Sandra Peters.