The complex nature and lifestyle of the chlamydia pathogen makes the development of a vaccine difficult. However, the development of such a vaccine is an international priority, and recently, a vaccine sponsor has completed a Phase I clinical trial producing promising results. Learn more about how Denmark’s Statens Serum Institut and Imperial College London collaborate to take on this major problem.
Chlamydia & Trichomoniasis Wreak Havoc Worldwide
With the outcomes published in The Lancet Infectious Diseases, the time is now to develop a disease. The World Health Organization (WHO estimates over 1 million new infections with four curable sexually transmitted diseases—chlamydia, gonorrhea, syphilis and trichomoniasis—acquired every day. This represents over 131 million annual infections—chlamydia represents the most common sexually transmitted bacterial disease. If left untreated, the infection can lead to chronic pelvic pain and tubal factor infertility as well as ectopic pregnancy.
Moreover, C. trachomatis infection, associated with greater susceptibility to other sexually transmitted diseases (especially gonorrhea and HIV), poses a greater risk if the infection is spread during pregnancy—introducing risks for miscarriage, stillbirth and preterm birth by either direct foetal infection, placental damage or severe mental illness. In males, C. trachomatis is associated with epididymitis and in both male and female the infection can trigger arthritis in a minority of cases.
National Treatment Programs Have Failed
Overall, national treatment programs have failed to move the needle of progress. Why? It could very well be that people infected with chlamydia develop either partial or temporary natural immunity to the pathogen, however until now, no previous vaccines for genital chlamydia have undergone clinical trials. Moreover, it is extremely difficult to change sexual lifestyle practices. People seem to keep making the same mistakes (e.g. unprotected sexual interaction, etc.).
The Investigational Vaccine
Statens Serum Institut, the sponsor, shares their vision for this vaccine that targets the bacterium immediately once it enters the genital tract. The sponsor designed the vaccine, known as CTH522, that elicits both cell-mediated and humoral immunity. The first line of defense is by neutralizing antibodies, and reducing initial infectious load—and once the bacteria are intracellular, they are targeted by bactericidal cell-mediated immune response.
The first-generation vaccine candidate—again CTH522—was based on the major outer membrane protein of the C trachomatis bacterium, has now completed a Phase I clinical trial.
The Clinical Trial
The study, officially titled as “A Phase I First in Human, Double-blind, Parallel, Randomized and Placebo Controlled Clinical Trial of the Safety of SSI’s Adjuvanted Chlamydia Vaccine CTH522 in Healthy Women Aged 18 to 45 Years,” was a Phase I fist-in-human, double blind, parallel and placebo controlled trial of SSI’s adjuvanted chlamydia vaccine CTH522: CTH522-CAF01 (CAF01 is an adjuvant system) and CTH522-AI(OH)3. The trial was conducted at Imperial College Research site in the United Kingdom. The subjects were randomly assigned one of the following three treatment groups in ratio of 3:3:1. The trial consisted of 10 visits and 5 telephonic interviews. A total of 35 patients were targeted and the duration of the study was July 2016 to July 2017.
The trial aimed to assess the safety and ability to provoke an immune response to the CTH522 chlamydia vaccine. As reported by Health Europa, 35 women, not infected with chlamydia, were included in the trial. The vaccine was deemed safe and all the women that participated in the trial developed an immune response against chlamydia.
The study team collected blood samples which were collected and demonstrated that all vaccinated women had generated specific antibodies and T-cells targeting chlamydia. During the trial it was revealed that high levels of antibodies were discovered in mucous secretion, including the special mucosal antibody IgA, which is known to block chlamydia early in the course of infection.
The study involved the sponsor (Statens Serum Institut), NIHR/Wellcome Trust Imperial Clinical Research Facility, Hammersmith Hospital, London and collaborator and main research site Imperial College London.
European Regional & Global Collaboration
The TracVac consortium works towards eliminating the global problem of blinding trachoma through the development of a vaccine. The organization strives to achieve two main objectives, including 1) generate a vaccine that protects against the bacterial strains causing ocular Chlamydia trachomatis infections; and 2) develop an immunization protocol for optimal mucosal immunity. VicPath, focused on the development of much-needed technological infrastructure in Europe—coupled with education and training of young investigators—promoting the development of innovative, protective and safe vaccines for future clinical use.
A new Planned Trial
A new Statens Serum Institut is planning more clinical development before this vaccine can be submitted for approval and marketed. Next year, Statens Serum Institut is planning a Phase 2A study, to be conducted in collaboration with researchers at Imperial College London. Upon completion of this study, the sponsor would plan an efficacy trial—e.g. a placebo-controlled trial with half the subjects receiving the active vaccine and half a placebo vaccine. The study would be performed in groups already at risk for infection and the trial would need a large enough group to detect a difference in the number of detected infections between those on active or placebo vaccine (estimated between 500 to a couple thousand).
About Statens Serum Institut
State Serum Institut (SSI) is a Danish sector research institute located on the island of Amager in Copenhagen. Its purpose is to combat and prevent infectious diseases, congenital disorders and threats from weapons of mass destruction. Founded in 1902 in a set of barracks, it is now expanded to much more than its original size and now represents one of Denmark’s largest research institutions in the health sector. 20% of its revenues are used for Research and Development and Danish and International funds contribute around 100 million DKK.
Administratively, the State Serum Institut sorts under the Danish Ministry of Health and Prevention.
Sonya Abraham, Imperial College London