The study of a novel oral vaccine that could protect against chlamydia infection has been awarded approximately $11 million in National Institutes of Health funding over five years through a cooperative agreements research project grant, known as a U01 grant.
“We are excited about receiving the U01 award because it will enable us to move our basic microbiology and immunology bench research work closer to developing a medically significant reagent for ‘making human lives better,’ our institution’s overall mission,” said Guangming Zhong, MD, PhD, professor of microbiology, immunology and molecular genetics with the Joe R. and Teresa Lozano Long School of Medicine at The University of Texas Health Science Center at San Antonio (UT Health San Antonio), and principal investigator of the study.
Severe complications
Chlamydia is the most reported sexually transmitted disease and affects about 4 million people in the United States each year, according to the Centers for Disease Control and Prevention. And yet, while there are vaccines for other sexually transmitted infections including HPV, hepatitis A and hepatitis B, there is none for chlamydia.
The infection often is left untreated due to the lack of specific symptoms. Untreated chlamydial infections can lead to severe complications including pelvic inflammatory disease, infertility and ectopic pregnancy.
Zhong said the prospective vaccine, called intrOv, came about after several years of persistent effort studying chlamydial pathogenic mechanisms in mice.
While investigating mouse-adapted chlamydia, the team accidently found that genital chlamydia that spread to the gastrointestinal tract established long-standing colonization.
Protective immunity
From there, they tried an oral inoculation of chlamydia to the GI system and found that it became not only non-pathogenic but also offered protective immunity against subsequent infection in other tissues including the genital tract and airways.
This surprising finding, Zhong said, led them to conclude that an oral delivery of chlamydia could serve as a vaccination against the infection. The team then created mutant versions of the infection that could no longer cause disease but could induce transmucosal protection.
One of these attenuated mutants, intrOv, included unique qualities viable for cross-species translation to the human pathogen of chlamydia.
All 15 serotypes
“Since the human pathogen chlamydia has more than 15 serotypes, developing a vaccine against all 15 serotypes is challenging,” Zhong said. “Using the mouse-adapted, chlamydia-bases vaccine intrOv to cover all 15 serotypes is a nice surprise.”
This grant supports the production of investigative new drug-enabling data for moving the oral chlamydia vaccine to Phase I trials.
“We will optimize the immunization regimens, identify protection immune correlates in mouse models and validate the vaccine efficacy in pigs and non-human primates,” Zhong said.
If all goes well at that stage, the team will file an Investigational New Drug, or IND, application with the Food and Drug Administration to advance the vaccine to clinical trials by the end of the grant’s time frame.
Oral vaccine
Back in 2022, UT Health San Antonio was granted an exclusive global license to allow Ohio biopharmaceutical company Blue Water Vaccines Inc. to develop Zhong’s findings into an oral vaccine for chlamydia.
Study collaborators from the Department of Microbiology, Immunology and Molecular Genetics at UT Health San Antonio include Zhenming “Jack” Xu, PhD, and Nu Zhang, PhD, who will provide B cell and T cell expertise.
Other collaborators include Pat Frost, DVM, and Marie-Claire Gauduin, PhD, primate genital-tract infection experts with Texas Biomedical Research Institute; Yufeng Wang, PhD, bioinformatics expert with The University of Texas at San Antonio; Luis M de la Maza, MD, PhD, with the University of California at Irvine; Huizhou Fan, MD, PhD, with Rutgers University; Harlan Caldwell, PhD, chief of chlamydial diseases section at the National Institute of Allergy and Infectious Diseases, NIAID; Robert Brunham, MD, with the University of British Columbia; and William Geisler, MD, MPH, from the University of Alabama.
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