The first ever early clinical trial for a vaccine for genital chlamydia has shown it to be safe and effective at provoking an immune response. The latest findings, from a randomised controlled trial of 35 healthy women led by Imperial College London and the Statens Serum Institut in Copenhagen, demonstrate promising early signs of what could be an effective vaccine against chlamydia.
The infection is the most common bacterial sexually transmitted infection (STI) worldwide and it can lead to infertility.
The researchers highlight that the work is ‘important first step’ but add that further trials are now needed to determine whether the immune response provoked by the vaccine will effectively protect against chlamydia infection.
Professor Robin Shattock, head of mucosal infection and immunity within the department of infectious disease at Imperial said: “The findings are encouraging as they show the vaccine is safe and produces the type of immune response that could potentially protect against chlamydia. The next step is to take the vaccine forward to further trials, but until that’s done, we won’t know whether it is truly protective or not.”
Chlamydia trachomatis is one of the most prevalent bacterial STIs, representing a major global health burden, with 131m new cases occurring each year. However, as many as 3 out of 4 infections are symptomless, so the number of cases is likely to be underestimated. National screening programmes and antibiotic treatment have failed to reduce infection rates, and the highest number of new cases are found in teenagers and young adults.
While infection can often be treated with antibiotics, complications can include inflammation, infertility, ectopic pregnancy, arthritis and even an increased susceptibility to other STIs, including HIV.
“The major issue with chlamydia is the long-term consequences,” explained Shattock. “It is very treatable if identified, but as many people don’t have symptoms it can be missed, and the biggest problem is that it can go on to cause infertility in women.”
He added: “One of the problems we see with current efforts to treat chlamydia is that despite a very big screening, test and treat programme, people get repeatedly re-infected. If you could introduce a protective vaccine, you could break that cycle.”
In the latest trial, researchers compared two different formulations of the new vaccine to examine which would perform better. The 35 women not infected with chlamydia included in the trial were randomly assigned to three different groups: 15 participants received the vaccine with liposomes, 15 received the vaccine with aluminium hydroxide, and 5 received saline solution (placebo).
In total, participants received five vaccinations with three intramuscular injections in the arm over several months, followed by two intranasal boosts.
Both formulations of the vaccine provoked an immune response in 100% of participants, whereas no participants in the placebo group achieved an immune response.
Although both formulations of the vaccine were found to provoke an immune response, the added liposomes consistently performed better and produced more antibodies, so the authors suggest this formulation should be pursued for further clinical development.
The group is now planning phase 2 trials.
Background: Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime–boost immunisation schedule.
Methods: This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19–45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 μg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 μg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109.
Findings: Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1·000). Both CTH522:CAF01 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunisations, whereas no participants in the placebo group seroconverted. CTH522:CAF01 showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile compared with CTH522:AH.
Interpretation: CTH522 adjuvanted with either CAF01 or aluminium hydroxide appears to be safe and well tolerated. Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development.
Funding: European Commission and The Innovation Fund Denmark.
Sonya Abraham, Helene B Juel, Peter Bang, Hannah M Cheeseman, Rebecca B Dohn, Tom Cole, Max P Kristiansen, Karen S Korsholm, David Lewis, Anja W Olsen, Leon R McFarlane, Suzanne Day, Sara Knudsen, Kjersti Moen, Morten Ruhwald, Ingrid Kromann, Peter Andersen, Robin J Shattock, Frank Follmann