Tulane receives $4 million to develop treatment that could protect against multiple infections within hours

It sounds like something out of science fiction: a pill or nasal spray that could potentially protect someone against the flu — or almost any other infection — within hours of taking it.

That is the idea behind a new technology being developed by Tulane University researchers who have received a $4 million contract from the U.S. Department of War’s Defense Threat Reduction Agency to create a fast-acting, broad-spectrum defense against infectious diseases.  

Unlike traditional vaccines, which are designed to protect against specific pathogens and can take weeks to generate immunity, the experimental treatment — called T-prop — is designed to temporarily put the body’s first line of immune defense on high alert. The goal is to provide rapid protection against a wide range of viruses and bacteria, including unfamiliar pathogens that could emerge during a pandemic or biological emergency.

“You could give it ahead of time — maybe a day, maybe even a few hours — and potentially protect someone against whatever pathogen they might encounter,” said James McLachlan, associate professor of microbiology and immunology at Tulane University School of Medicine. “The idea is that you give one treatment and provide protection across the board.”

McLachlan and Lisa Morici, professor and interim chair of the Department of Microbiology and Immunology at Tulane School of Medicine, are leading the four-year project.

T-prop is based on outer membrane vesicles, or OMVs, microscopic particles naturally released by bacteria. The Tulane team has spent years developing the platform for vaccines and other immune-based therapies. In this application, however, the OMVs are used alone — without an antigen from a specific virus or bacteria — to stimulate the innate immune system.

Vaccines generally train the adaptive immune system to recognize a particular pathogen and build lasting immune memory. T-prop takes a fundamentally different approach. It is designed to temporarily activate the innate immune system, the body’s rapid first line of defense, so it is ready to respond when an infection arrives.

“It’s essentially turning the alarm on,” McLachlan said. “You induce an immune response in the nose or lungs, and the idea is that it’s enough to protect you for a period of time.”

How quickly that protection can be established — and how long it lasts — are among the central questions the researchers will investigate.

Preliminary studies have produced striking results. In one experiment, mice treated 24 hours before exposure to a highly lethal dose of influenza were fully protected, while substantial protection remained when the treatment was given 48 or 72 hours beforehand.

“Now we’re trying to determine how long that protection lasts, how far in advance we can give it and exactly what the immune system is doing to produce that protection,” McLachlan said.

The researchers do not yet know whether T-prop prevents infection entirely, rapidly clears the pathogen from the body or reduces it enough to prevent illness. Determining that will be another focus of the project.

The researchers will also test T-prop against multiple bacterial and viral pathogens and study different doses, treatment schedules and routes of administration.

For respiratory threats, the technology could eventually be formulated as a nasal spray. For pathogens entering through the digestive tract, it could potentially be delivered as a tablet or slow-release oral formulation.

A major scientific challenge will be finding the balance between activating enough of an immune response to prevent disease without generating excessive inflammation that could damage healthy tissue.

“Inflammation in the mucosa isn’t always a good thing,” Morici said. “You don’t want your lungs inflamed, and you don’t want your gut inflamed. If we’re trying to induce an inflammatory response that is protective, we want to make sure it is exactly that — protective and not detrimental.”

Morici said previous studies of Tulane’s OMV platform in nonhuman primates have shown inflammation returns to normal within roughly 24 to 72 hours after treatment ends.

That temporary response is an important feature of the technology. Unlike a vaccine, T-prop is not intended to create lasting immune memory against a particular pathogen. Instead, researchers envision activating the innate immune system for a defined period when someone faces heightened risk and allowing the response to subside when the threat has passed.

The OMVs are also noninfectious and nonreplicating, potentially offering an advantage over other approaches researchers have explored to generate broad, nonspecific immune protection. The ultimate goal is to generate the safety and efficacy evidence needed to position T-prop for human clinical trials.

While the immediate application envisioned is protecting military personnel, McLachlan sees potentially much broader uses. Someone whose spouse has the flu, for example, might one day receive a short-term preventive treatment rather than waiting to become infected and then taking an antiviral medication.

“Instead of doing this after the fact, when you get the flu and then take a drug that makes you less sick, could we prevent you from getting sick at all?” McLachlan said. “That’s ultimately where we envision this going.”