Longhorn Vaccines Develops Sepsis Vaccine Targeting Key Toxins

Longhorn Vaccines and Diagnostics has developed a promising new sepsis vaccine utilizing a composite peptide approach that targets three major toxins: lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan. Designed to prevent sepsis and improve the effectiveness of existing antibiotics, this vaccine may also hold potential for treating a range of inflammatory diseases such as Alzheimer's, Parkinson's, heart disease, and cancer. The vaccine's antibodies are being engineered for an extended half-life, increasing their potential for longer-lasting efficacy.

Jeff Fischer, MBA, co-founder and president of Longhorn Vaccines, emphasized the significance of this breakthrough. “Sepsis prevention has always been something we've been working toward, and I think our composite peptide approach has brought us closer to that success.

The vaccine combines LPS, LTA, and peptidoglycan into a single, composite peptide. This combination uniquely addresses both gram-positive and gram-negative bacterial infections, which are major contributors to sepsis. Fischer explained the difficulties with past approaches: “At that time, we were focusing on a component of the bacterial cell wall called lipoteichoic acid (LTA), which is found on gram-positive bacteria. One of the challenges with this approach was that it only covered gram-positive species, while gram-negative bacteria are also a major cause of sepsis.”

In the 1980s, research on LPS—a toxin from gram-negative bacteria—had failed in clinical trials, but Fischer's team was able to combine LPS and LTA into one vaccine. Adding peptidoglycan, a common component in both types of bacteria, strengthened the approach. Fischer elaborated, “We were able to combine LPS and LTA into a single vaccine, and there was another key factor that gave us confidence: adding peptidoglycan, a component of the cell wall found in both gram-positive and gram-negative bacteria. Peptidoglycan is released during bacterial cell death and the process of infection, contributing to inflammation that can lead to sepsis.”

This composite peptide vaccine has the potential to reduce sepsis-related inflammation by targeting the three main toxins involved. According to Fischer, “By combining LTA, LPS, and peptidoglycan into a composite peptide vaccine, we were able to target the three main toxins that contribute to sepsis-related inflammation. The antibodies generated by this vaccine not only reduced the toxins but also helped kill the bacteria. With this approach, we felt we had an opportunity not just to treat sepsis after it occurred but potentially to prevent it altogether.”

The vaccine may also help tackle the growing challenge of antibiotic resistance. Fischer noted, “This approach also allows us to use fewer antibiotics, which is significant given the growing issue of antibiotic resistance. In fact, this vaccine may make current antibiotics, which have become less effective, more effective again—by working in conjunction with the antibodies to clear the bacteria and the circulating toxins.”

As the research progresses, Fischer and his team are uncovering broader implications for the vaccine. The same toxins—LPS, LTA, and peptidoglycan—are implicated in a variety of inflammatory diseases, which are associated with conditions like Alzheimer's, Parkinson’s, heart disease, and certain cancers. Fischer shared his thoughts on the broader impact: “As we’ve continued our research and explored the idea of clearing these toxins, we've realized that LPS, LTA, and peptidoglycan may be implicated in many other significant diseases due to the inflammation they cause. Because these toxins are constantly released when bacteria enter the bloodstream, whether from the gut or urinary tract infections, they contribute to systemic inflammation throughout the body.”

Fischer believes the approach could be a powerful tool for treating a wide array of inflammatory diseases. “The key advantage is that the body has no use for these toxins, so by eliminating them, there’s no real threat to the host. We're not downregulating something essential or cutting back on beneficial inflammation, such as cytokines that help fight infection. Instead, we’re naturally downregulating the immune response by removing the toxins that are driving excessive inflammation.”

Longhorn Vaccines is moving forward with the development of this innovative vaccine. Fischer concluded, “We’re very excited about this work and are moving it forward as quickly as possible. We hope to have more data to share with the scientific community soon.”

Part 1 of our interview with Fischer on their universal influenza vaccine approach here: New Peptide Vaccine for Universal Influenza Protection