In the JournalsPerspective

Chlamydia vaccine shows promise in phase 1 trial

A chlamydia vaccine candidate showed promise in a first-in-human phase 1 trial, demonstrating safety and tolerability and provoking an immune response, researchers reported in The Lancet Infectious Diseases.

According to the CDC, chlamydia is the most commonly reported STI in the United States, with almost half of the more than 1.7 million cases diagnosed in 2017 occurring in females aged 15 to 24 years. In their report on the phase 1 trial, Sonya Abraham, MD, clinical senior lecturer in rheumatology and general internal medicine at Imperial College London, and colleagues noted that it is the most commonly transmitted bacterial STI worldwide.

Despite screening programs and antibiotic treatments, the incidence of chlamydia has not gone down, Abraham and colleagues said.

In the double-blind, parallel, randomized, placebo-controlled trial, they assessed the safety and immunogenicity of a novel chlamydia vaccine based on CTH522, “a recombinant engineered version of the C. trachomatis major outer membrane protein (MOMP), comprising heterologous immunorepeats from four genital C. trachomatis serovars.”

They conducted the trial at Hammersmith Hospital in London, enrolling 35 healthy women aged 19 to 45 years. Between Aug. 15, 2016, and Feb. 13, 2017, they randomly assigned 15 women to receive CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), 15 to receive CTH522 adjuvanted with aluminum hydroxide (CTH522:AH) and five to receive a placebo. At months 0, 1 and 4, the participants received intramuscular injections of 85 g adjuvanted vaccine or placebo. This was followed by two intranasal administration of 30 g unadjuvanted vaccine or placebo at 4 1/2 and 5 months.

According to the study, no serious adverse events were observed. All of participants in each adjuvanted vaccine group and 60% of participants in the placebo group reported mild local injection-site reactions. Compared with placebo, intranasal boosting was not associated with a higher frequency of local reactions, the researchers said.

After five immunizations, both CTH522:CAF01 and CTH522:AH induced anti-CTH522 immunoglobulin G seroconversion in 100% of participants compared with no seroconversions in the placebo group, Abraham and colleagues reported.

The researchers noted “accelerated seroconversion, increased IgG titers, an enhanced mucosal antibody profile and a more consistent cell-mediated immune response” with CTH522:CAF01 compared with CTH522:AH.

“In conclusion, we show that CTH522:CAF01 and CTH522:AH are both safe and immunogenic,” Abrahams and colleagues wrote. “The promising immunogenicity profile of CTH522:CAF01 warrants further clinical development, and preparation of a phase 2 dose optimization study is currently ongoing.”

In a related editorial, Taylor B. Poston, PhD, MPH, a postdoctoral researcher at the University of North Carolina at Chapel Hill, and Toni Darville, MD, chief of pediatric infectious diseases and distinguished professor of pediatrics and microbiology & immunology at the University of North Carolina School of Medicine, explained that a vaccine to prevent infections caused by C. trachomatis would have an “enormous” impact on public health.

“Findings from this phase 1 trial might also help guide the development of vaccines for other mucosal pathogens,” they wrote. “Although clinical vaccine testing for chlamydia is in its infancy, this trial suggests optimism for the future.” – by Marley Ghizzone

Disclosures: Abraham, Darville and Poston report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

A chlamydia vaccine candidate showed promise in a first-in-human phase 1 trial, demonstrating safety and tolerability and provoking an immune response, researchers reported in The Lancet Infectious Diseases.

According to the CDC, chlamydia is the most commonly reported STI in the United States, with almost half of the more than 1.7 million cases diagnosed in 2017 occurring in females aged 15 to 24 years. In their report on the phase 1 trial, Sonya Abraham, MD, clinical senior lecturer in rheumatology and general internal medicine at Imperial College London, and colleagues noted that it is the most commonly transmitted bacterial STI worldwide.

Despite screening programs and antibiotic treatments, the incidence of chlamydia has not gone down, Abraham and colleagues said.

In the double-blind, parallel, randomized, placebo-controlled trial, they assessed the safety and immunogenicity of a novel chlamydia vaccine based on CTH522, “a recombinant engineered version of the C. trachomatis major outer membrane protein (MOMP), comprising heterologous immunorepeats from four genital C. trachomatis serovars.”

They conducted the trial at Hammersmith Hospital in London, enrolling 35 healthy women aged 19 to 45 years. Between Aug. 15, 2016, and Feb. 13, 2017, they randomly assigned 15 women to receive CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), 15 to receive CTH522 adjuvanted with aluminum hydroxide (CTH522:AH) and five to receive a placebo. At months 0, 1 and 4, the participants received intramuscular injections of 85 g adjuvanted vaccine or placebo. This was followed by two intranasal administration of 30 g unadjuvanted vaccine or placebo at 4 1/2 and 5 months.

According to the study, no serious adverse events were observed. All of participants in each adjuvanted vaccine group and 60% of participants in the placebo group reported mild local injection-site reactions. Compared with placebo, intranasal boosting was not associated with a higher frequency of local reactions, the researchers said.

After five immunizations, both CTH522:CAF01 and CTH522:AH induced anti-CTH522 immunoglobulin G seroconversion in 100% of participants compared with no seroconversions in the placebo group, Abraham and colleagues reported.

The researchers noted “accelerated seroconversion, increased IgG titers, an enhanced mucosal antibody profile and a more consistent cell-mediated immune response” with CTH522:CAF01 compared with CTH522:AH.

“In conclusion, we show that CTH522:CAF01 and CTH522:AH are both safe and immunogenic,” Abrahams and colleagues wrote. “The promising immunogenicity profile of CTH522:CAF01 warrants further clinical development, and preparation of a phase 2 dose optimization study is currently ongoing.”

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In a related editorial, Taylor B. Poston, PhD, MPH, a postdoctoral researcher at the University of North Carolina at Chapel Hill, and Toni Darville, MD, chief of pediatric infectious diseases and distinguished professor of pediatrics and microbiology & immunology at the University of North Carolina School of Medicine, explained that a vaccine to prevent infections caused by C. trachomatis would have an “enormous” impact on public health.

“Findings from this phase 1 trial might also help guide the development of vaccines for other mucosal pathogens,” they wrote. “Although clinical vaccine testing for chlamydia is in its infancy, this trial suggests optimism for the future.” – by Marley Ghizzone

Disclosures: Abraham, Darville and Poston report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Jeanne M. Marrazzo

    Jeanne M. Marrazzo

    There is sound scientific consensus that widespread screening for Chlamydia trachomatis in women has effected population-level declines not only in prevalence of infection but in adverse reproductive health sequelae, especially ectopic pregnancy and symptomatic pelvic inflammatory diseases. However, the potential impact of screening is limited for two reasons. First, nucleic acid-based amplification testing can be costly to implement and conduct, especially in settings with limited resources. Second, even with good screening uptake, the declines in chlamydia prevalence experienced in the early days of implementation seem to have stalled. We don’t understand why, but some have suggested that treatment of asymptomatic disease actually interrupts the natural and ultimately protective immune response to this pathogen. Thus, the findings that a new vaccine (CTH522) based on the major outer membrane protein and formulated with two different adjuvants provoked an immune response in all immunized participants (albeit only 15) are important. Whether this particular response will confer protective immunity remains to be seen. Nonetheless, as proof of principle, this finding informs a path forward for this very important effort.

    • Jeanne M. Marrazzo, MD, MPH
    • Infectious Disease News Editorial Board member
      Director, division of infectious diseases
      C. Glenn Cobbs, MD, Endowed Professor in Infectious Diseases
      University of Alabama at Birmingham School of Medicine

    Disclosures: Marrazzo reports no relevant financial disclosures.