Chlamydia Vaccine Appears Safe After Phase 1 Trial

Sonya Abraham, PhD

Officials are hoping to build on the success of a phase 1 clinical trial testing the safety and immunogenicity of a novel chlamydia vaccine.

A team of investigators, led by Sonya Abraham, PhD, Clinical Senior Lecturer in Rheumatology and General Internal Medicine at Imperial College London, found the recombinant protein subunit—CTH522—was safe in a prime-boost immunization schedule in a phase 1, first-in-human, double-blind, parallel, randomized, placebo-controlled trial at the Hammersmith Hospital in London.

The trial included 35 healthy women between 19-45 years old from August 15, 2016-February 13, 2017 randomly assigned to 3 different groups—CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminum hydroxide (CTH522:AH), or a placebo (saline).

Each participant received 3 intramuscular injections of 85 µg of the vaccine or placebo to the deltoid region of the arm, 1 and 4 months after an initial injections, followed by 30 µg of the unadjuvanted vaccine or placebo in each nostril at 4.5 and 5 months.

“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 2 vaccine groups and in 3 (60%) of 5 participants in the placebo group (P =.053 for both comparisons),” the authors wrote. “Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in 7 (47%) of 15 participants in the active treatment groups vs 3 (60%) of 5 in the placebo group; P =1.0).”

The most frequent reported local reaction were injection-site pain, tenderness, and movement impairment. However, 88-93% of the events reported by each of the 3 groups was labeled as mild, lasting a median of 2-4 days for all groups.

Both vaccination groups induced anti-CTH522 IgG seroconversion in 100% of participants after 5 immunization, while no member of the placebo group seroconverted. CTH522:CAF01 also showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response when compared with CTH522:AH.

“CTH522 adjuvanted with either CAF01 or aluminum hydroxide appears to be safe and well tolerated,” the authors wrote. “Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development.”

The new vaccine incorporates a key neutralizing epitope expressed in serotypes D—G, which are the most prevalent serotypes in clinical circulation, representing close to 90% of genital C trachomatis infections.

The vaccine molecule also contains a large MOMP segment shared among all genital tract isolates, known to contain both shared B-cell and T-cell epitopes.

Future clinical efficacy trials could provide some level of protection against the remaining 10% of clinically relevant serovars.

According to the World Health Organization (WHO), there are an estimated 131 million annual incident infections of chlamydia, making it the most common sexually transmitted disease. Untreated or repeated infections are the main drivers of chlamydia-associated morbidity, accounting for approximately 370,000 disability-adjusted life years annually.