The first ever vaccine against genital chlamydia was safe and immunogenic in healthy women volunteers, a small phase I study found.
CTH522, a novel vaccine against chlamydia, given both as an adjuvanted intramuscular vaccine and an unadjuvanted intransal vaccine booster, was mostly safe with no serious related adverse events and only mild local injection-site reactions, reported Peter Andersen, PhD, of Statens Serum Institut in Copenhagen, Denmark, and colleagues.
Moreover, the vaccine induced seroconversion in all 30 participants in the two treatment groups, the authors wrote in The Lancet Infectious Diseases.
“Given the impact of the chlamydia epidemic on women’s health, reproductive health, infant health through vertical transmission, and increased susceptibility to other sexually transmitted diseases, a global unmet medical need exists for a vaccine against genital chlamydia,” Andersen said in a statement.
While chlamydia is the most common bacterial sexually transmitted infection worldwide, the authors said that several strategies — including diagnostic testing, effective treatment, and targeting screening and treatment programs — have failed to curb the epidemic. But they added that no vaccine against Chlamydia trachomatis has been in clinical trials since the 1960s, when there was a series of trials for a vaccine against ocular chlamydia.
They described the vaccine antigen, CTH522 as a “recombinant engineered version of the C. trachomatis major outer membrane protein.” In this trial, adjuvants included either cationic liposomal adjuvant CAF01 or aluminum hydroxide, a form of aluminum often used as a vaccine adjuvant.
Participants were healthy women ages 19-45 who were not pregnant and agreed to two approved forms of contraception or to abstain from sexual intercourse during the trial period. These women had a BMI of <35, no history of pelvic inflammatory disease or other significant gynecological diseases, and tested negative for HIV, hepatitis B, hepatitis C, syphilis, gonorrhea, and C. trachomatis.
The dosing schedule was three intramuscular doses of CTH522 with one of the two adjuvants at 0, 1 and 4 months, followed by two intranasal boosts (one in each nostril) of unadjuvanted CTH522 at 4.5 and 5 months, or comparable dosing with placebo.
Overall, data from 35 women — 15 in the CTH522:CAF01 group and 15 in the CTH522:AH group; five in the placebo group — were included in an intention-to-treat analysis, though the authors noted two participants in the CTH522 group withdrew due to scheduling issues and one in the CTH522:AH group withdrew after the second dose due to low hemoglobin concentrations from menorrhagia and study-related blood sampling.
Safety was the primary outcome, and the most common local reactions were injection site pain, tenderness, and movement impairment, though nearly all participants reported these were mild symptoms lasting a median of 2-4 days. While the authors found that all participants had a local injection site reaction, which occurred at a higher, non-significant frequency in the placebo group. There was no difference between the groups with intranasal site reactions (7/15 participants in each treatment group vs 3/5 in the placebo group).
There were 13 treatment-emergent adverse events — five in the CTH522CAF01 group, six in the CTH522:AH group, and two in the placebo group. These included muscular skeletal stiffness, oropharyngeal pain, and nasopharyngitis.
Immunogenicity was a secondary outcome, and all 15 participants in both groups achieved a higher than four-fold IgG seroconversions after the three intramuscular immunizations, though the authors noted “the nasal booster immunizations did not increase systemic antibody concentrations.”
As for the next steps, an accompanying editorial by Taylor Poston, PhD, MPH, and Toni Darville, MD, both of the University of North Carolina at Chapel Hill, agreed that a vaccine to prevent C. trachomatis infection would have “enormous public health and economic impact.” But they urged caution about using chlamydia genital infection as an endpoint to ascertain efficacy, saying it would “involve interval testing in placebo-treated versus vaccinated women.”
“Although conceptually straightforward, women at highest risk for infection will need to be enrolled, and many will possibly have some pre-existing immunity from previous infections, given the high prevalence of chlamydia among sexually active adolescent girls and young women,” the editorialists wrote. “Thus, careful evaluations of baseline immune response will be needed to ensure treatment groups are comparable.”
They also suggested additional efficacy endpoints, such as non-invasive biomarkers of chlamydia upper genital tract infection and inflammation.
Andersen and colleagues also had an eye towards the future, noting that of the two adjuvanted vaccines, CTH522:CAF01 “showed accelerated seroconversion, increased IgG [titers], an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response.” Preparation of a phase II dose optimization study is currently ongoing, they said.
The study was supported by the European Commission through the ADITEC consortium contract and The Innovation Fund Denmark.
Andersen and two co-authors disclosed being co-inventors on a patent application on vaccines against chlamydia. All rights have been assigned to Statens Serum Institut, a Danish not-for-profit institute under the Ministry of Health.
Poston and Darville disclosed no relevant relationships with industry.