Chlamydia is the most common sexually transmitted bacterial infection globally. However, national programs for screening and treatment have been suboptimal in controlling incident infections. Untreated or repetitive infections with Chlamydia trachomatis frequently result in pelvic inflammatory disease in 1 in 6 women, and approximately half of infants born to mothers with chlamydia will develop congenital infection; such infection is further responsible for 370,000 disability-adjusted life-years annually.
According to study results published in the Lancet Infectious Disease, researchers at the National Institute for Health Research Imperial Clinical Research Facility at Hammersmith Hospital in London have demonstrated immunogenic responses in the first phase 1 human trials of a novel vaccine for the prevention of C trachomatis infection, based on the recombinant protein subunit CTH522 of the bacteria. The researchers included 35 healthy women aged 19 to 45 years who were not pregnant; had no history of chlamydia, gonorrhea, pelvic inflammatory disease/other significant gynecologic disease, HIV, hepatitis B, hepatitis C, or syphilis; and who agreed to use 2 approved forms of contraception and to refrain from sexual intercourse for the trial period. Participants were randomly assigned in a 3:3:1 ratio to receive either CTH522:CAF01 (CTH522 adjuvanted with CAFO1 liposomes), CTH522:AH (CTH522 adjuvanted with aluminum hydroxide), or placebo, followed by 2 intranasal doses of unadjuanted CTH522 or placebo.
The primary outcome of the study was safety of the vaccine, and researchers noted that no serious adverse events related to the vaccine occurred during the trial. The most commonly reported adverse event reported was local injection-site reaction (pain, tenderness, and/or decreased range of movement); this occurred in all participants in both treatment groups. There was also no significant difference between the 3 groups in reports of systemic adverse reactions.
The secondary outcome was the induction of humoral immunogenicity, predefined as a >4-fold IgG seroconversion postvaccination: 100% of the CTH522:CAF01 group and 93% of the CTH522:AH group achieved the marker of immunogenicity. None of the participants in the placebo group attained seroconversion. In addition, the intranasal CTH522 post-immunization booster did not increase concentrations of systemic antibodies. Post-hoc analysis demonstrated a strong immune response after the first vaccination in both treatment groups, which was increased with each administration.
Of note, though both vaccines showed significant efficacy, CTH522:CAF01 demonstrated a reliably superior, though non-statistically significant difference in immunogenicity compared with CTH522:AH. After the third administration in the vaccine series, CTH522:CAF01 induced a 5.6-fold higher median titer compared with CTH522:AH (P =.0091); this remained 2.5-fold higher than CTH522:AH throughout the trial period. Further, though both treatment groups showed an increase in neutralizing antibody concentrations after the 3rd dose of each vaccine, CTH522:CAF01 demonstrated a higher mean titer compared with CTH522:AH (254.1 vs 107.4). In addition, vaginal IgG concentrations increased 16.4-fold in the CTH522:CAF01 group postvaccination, and mucosal IgA concentrations were increased in the CTH522:CAF01 group after the intranasal booster. The CTH522:CAF01 vaccine was also associated with a stronger increased in vaccine-specific cell-mediated response compared with the CTH522:AH vaccine, though this difference was not statistically significant.
One of the study authors, Professor Peter Andersen, from Statens Serum Institut, Denmark, concluded that “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.”
Abraham S, Juel HB, Bang P, et al. Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial [published online August 12, 2019]. Lancet Inf Dis. doi:10.1016/S1473-3099(19)30279-8