New ‘linked’ Chlamydia vaccine on the cusp of a breakthrough
Whenever Toni Darville, M.D., gives a presentation about one particular topic, she expects bewildered expressions on people’s faces. It’s not what she discusses that stirs confusion, but rather why someone in her role is even talking about the subject.
“People often seem surprised when I speak about chlamydia as a pediatric infectious disease physician,” said Darville, Distinguished Professor of Pediatrics and Microbiology & Immunology, division chief of Pediatric Infectious Diseases, and scientific director of the Children’s Research Institute at the UNC School of Medicine. “What many don’t realize is that chlamydia infections often begin during the teenage years, soon after young people become sexually active—and in some communities, studies have found that as many as 5 to 10% of ninth-grade students test positive.”
But when Darville begins to describe a first-of-its-kind vaccine candidate for chlamydia, the perplexed looks give way to intrigue. She is developing the vaccine with scientific collaborator Taylor Poston, Ph.D., an assistant professor of Pediatrics at the UNC School of Medicine, and leaders at clinical-stage biotechnology company Vaxcyte, Inc.
The technology is advancing rapidly, and if ultimately successful, the vaccine could one day be given as an intramuscular injection as part of the standard recommended series of immunizations for children. “The goal is that when kids go to their doctor’s office to get their HPV vaccine, they get their fertility vaccine for chlamydia, too,” said Darville.
Combatting chlamydia, the world’s leading bacterial STI
The team’s work on the vaccine targets a significant and often underrecognized public health challenge. Chlamydia is the most common bacterial sexually transmitted infection in the world, with approximately 128 million new infections occurring annually. In the U.S., an estimated 1.5 million people became infected in 2024. And chlamydia runs particularly rampant in what clinicians call the “Southern STI Belt,” including states like North Carolina, where infection rates are consistently elevated.
In family planning and adolescent health clinics, says Darville, as many as one in five individuals may test positive. And unlike some sexually transmitted infections, chlamydia cuts across socioeconomic lines, affecting individuals regardless of background or education. Its widespread reach is driven largely by the fact that 70% of infected people—especially women—experience no symptoms, allowing the disease to spread silently and persist undetected for months or even years.
The consequences of untreated chlamydia can be severe and long-lasting. The infection can spread into the female reproductive tract, causing pelvic inflammatory disease (PID) in more than 1 million American women annually. This can cause chronic pelvic pain, inflammation of the uterus, and scarring of the fallopian tubes. These complications routinely lead to reproductive challenges, making chlamydia the leading cause of preventable infertility worldwide. The costs of treating PID in the U.S. alone approach $2 billion annually. Even when infertility does not occur, chlamydial infection can increase the risk of ectopic pregnancy, a potentially life-threatening condition in which a fertilized egg implants outside the uterus.
“Only a minority of infected women experience bad complications,” said Darville. “But because the prevalence of the disease is so high, the number of women with severe outcomes adds up quickly.”
A new ‘linked’ vaccine design
Previous attempts to develop a chlamydia vaccine have fallen short because they did not generate a strong enough protective immune response. But thanks to Darville, Poston, and their industry and academic partners, this largely invisible infection with lifelong consequences may soon have a highly visible solution.
To develop the vaccine, Darville and Poston partnered with two co-investigators at Vaxcyte: Jeff Fairman, Ph.D., vice president of research and co-founder of the company, and James Rozzelle, Ph.D., senior staff scientist, who earned his doctoral degree at UNC-Chapel Hill. The innovative vaccine finds its roots in Darville’s research. For instance, in 2024, the team led by Darville received a $9.3 million grant from the National Institute of Allergy and Infectious Diseases to help develop a vaccine candidate.
“For many years, my lab has conducted studies to determine the response needed to drive protection against chlamydia,” she said, noting that combating chlamydia requires a different approach than most existing vaccines, which primarily work by generating antibodies. “We determined that a specific type of T cell response—CD4 interferon-gamma producing cells—is critical for clearing infection and preventing reinfection.”
Determining that the vaccine needed to generate chlamydia-specific T cells was one piece of the puzzle. But exactly which antigen—a component of the bacteria that trains the body to recognize and defend against the pathogen—would the team need to include in the vaccine to generate the most T cells? Darville’s lab found that a protein called Chlamydial Protease Activation Factor (CPAF) stood out: the most frequently recognized antigen among infected women and consistently triggered the strongest T-cell responses within individuals.
To generate a strong enough immune response, the team needed to pair the CPAF antigen with an immune agonist—an adjuvant that boosts the body’s immune reaction—while still avoiding unnecessary side effects. Poston tested a range of combinations in mouse models and found that one stood out: a Stimulator of Interferon Genes (STING) agonist. This adjuvant, provided by biotechnology company and manufacturer InvivoGen, produced the most robust immune response.
Rather than simply mixing the vaccine components—as is done with many traditional vaccines—Poston and Rozzelle developed a way to physically link the CPAF protein (the antigen) to the STING agonist (the immune stimulant). The result is a new “linked” vaccine platform that builds on established science while delivering a more targeted and potent immune response.
“Our approach is a hybrid of ideas from both traditional vaccines and newer immunotherapies,” said Poston. “Conjugate vaccines have been around for decades, but typically work by attaching a weak molecule, like a sugar on a bacterial surface, to a protein to help the body recognize it and generate an immune response. What we’ve done differently is take the concept of conjugation and apply it in a new way—by linking a chlamydia protein antigen directly to a STING agonist. This is designed to stimulate a much stronger T-cell response, not just antibodies, creating a new type of vaccine.”
This new linked design triggered a strong immune response across multiple mouse strains, including those that exhibit higher bacterial burdens and more severe, long-standing infections. “Across the strains we’ve tested, we’re eliciting responses at the high end of what’s been reported in the scientific literature,” said Poston. For example, in strains that routinely shed 1 million bacteria early after inoculation, the vaccine reduces the count to 10,000. “We’re excited because the vaccine appears to be both potent and well-tolerated.” The new vaccine design also requires far less immune agonist—about 80-fold less adjuvant than traditional methods—making it more practical to manufacture at scale and potentially safer for future clinical use.
Industry partnership supports scalability and path to market
The partnership with Vaxcyte is fruitful on multiple fronts. For one, the company uses a special technology — a cell-free protein synthesis platform — which uses biological machinery in a controlled, test-tube environment to produce proteins without relying on living cells. This means the team can consistently and efficiently produce the chlamydia protein (CPAF) used in the vaccine with high quality and uniformity, which is critical for large-scale manufacturing. “The cell-free transcription system from Vaxcyte escalated this to a scalable vaccine,” said Darville. “The technology allows the CPAF protein to be produced repeatedly with the same structure and stability, which is exactly what you need when you’re thinking about manufacturing at the scale of hundreds of millions to a billion doses.”
Teaming with Vaxcyte also sparked scientific approaches. Poston and Rozzelle worked together to apply two Nobel-prize-winning ideas developed by other scientists — click chemistry (a fast, precise way to “snap” molecules together) and the AlphaFold database (an AI tool that predicts protein shapes) — to optimize their own vaccine construct. When combining these with the Vaxcyte site-specific conjugation and cell-free protein synthesis technologies, the team produced a vaccine that has the characteristics suitable for large-scale development.
“Using this approach, we can directly and specifically design where we want the very small STING agonist molecules to attach to the CPAF protein,” said Poston. “From a manufacturing standpoint, that level of precision is a major advantage because it allows us to produce the same, consistent product every time.”
The Vaxcyte team also brings deep expertise in regulatory strategy and commercial scalability, subjects that many academic researchers aren’t as familiar with. For instance, the company works closely with the FDA and already has a pneumococcal vaccine in phase 3 clinical trials. This complementary partnership allows the Carolina scientists to stay focused on what they do best: designing and testing vaccines in the lab, while Vaxcyte helps guide the path toward clinical development and real-world use.
“I’m a physician-scientist, and Taylor is an immunologist, but our work has focused on preclinical research—we haven’t taken vaccines into human trials. So, the investigators at Vaxcyte have been excellent and complementary partners because they bring deep expertise in vaccine development and the regulatory process, including the extensive studies required for stability and safety, which are huge endeavors,” said Darville. “Having a partner with that experience has been incredibly valuable for us.”
“Combining UNC’s foundational research on T cell-mediated protection with Vaxcyte’s cell-free protein synthesis platform and conjugation expertise has produced a vaccine candidate with a meaningfully different mechanism of action than prior chlamydia approaches,” said Fairman. “The preclinical immune responses we are seeing reinforce our confidence in the linked-vaccine design, and we look forward to advancing this candidate toward clinical development.”
‘Threshold of a breakthrough’ for chlamydia patients
In 2023, Darville and Poston began working with the technology commercialization team at Innovate Carolina to manage intellectual property and strengthen industry partnerships. The two UNC-Chapel Hill scientists are co-inventors with Fairman and Rozzelle from Vaxcyte on the vaccine candidate technology, which is currently protected by pending patent applications in the United States and internationally.
“The heroes of this project are Toni Darville and Taylor Poston, whose tireless dedication in the lab has brought us to the threshold of a breakthrough,” said Dean Stell, associate director of the UNC Office of Technology Commercialization. “Our role is simply to support their vision by managing the patents and industry partnerships necessary to help move this promising work toward real-world impact for patients.”
In 2025, Innovate Carolina’s Institute for Convergent Science (ICS) provided the project with additional translational traction. ICS supports scientists like Darville and Poston through its AGILE grant program, which provides milestone-based funding designed to help research teams move promising discoveries toward practical applications. ICS and Innovate Carolina also connect investigators with industry partners, investors and commercialization resources that can help transform early-stage ideas into technologies that benefit society.
“The speed at which Toni, Taylor and their team are advancing their novel vaccine design toward clinical development is impressive,” said Greg Copenhaver, Ph.D., director of ICS and Chancellor’s Eminent Professor of Convergent Science. “The chlamydia vaccine project demonstrates how talented scientists can work with the Institute for Convergent Science to move technologies like an antigen-adjuvant fusion out of discovery and into the translational phase—accelerating ideas to reach commercial partners and ramp up the human impact potential.”
The ICS AGILE grant program provides the vaccine team with seed funding for technology development. The program also offers access to project management and entrepreneurial mentors, plus shared equipment and lab space where members of Darville’s and Poston’s lab team convene.
“We couldn’t have done this without the funding, but it’s not just the dollars from ICS that are important,” said Poston. “They purchased a brand new ELISpot Reader system that we use in the ICS lab space to quantify the T cell response to our vaccine. That equipment has been critical to our work because it provides greater precision and flexibility in the number of parameters we can test.” The team’s technicians also use a KingFisher automated extraction system in the ICS lab to perform DNA and RNA extractions—streamlining work that used to take a week to a couple of hours.
The project is a training ground for students—graduate, undergraduate and high school—who gain experience with vaccine design and testing. These learning opportunities often open new professional paths. In fact, two former undergraduate students from Darville’s and Poston’s lab now work as professional technicians on the project. Researchers from the ICS postdoctoral and professional development training program, which helps postdocs develop technical and business skills while working with ICS projects, also gained commercialization experience through exposure to the vaccine project.
The vaccine is approaching a critical milestone on the path to protecting patients. Following successful studies in mouse models at UNC-Chapel Hill, testing is now beginning in non-human primates at the University of California, Davis. And if those proceed successfully, as Darville and Poston anticipate, the vaccine could move into human clinical trials with Vaxcyte leading the path to clinical development.
“Just 15 years ago, we couldn’t have developed a vaccine that would work for chlamydia,” said Darville. “Now, we have the knowledge, technologies and molecular approaches needed to generate the kind of protective immune response people need.”
Note: This article originally ran on Innovate Carolina.