EXECUTIVE SUMMARY

Results of an early trial of a potential chlamydia vaccine indicate it is safe for use. While the vaccine, the first to reach Phase 1 clinical trial status, demonstrates promising early signs, further studies are needed to determine whether the immune response fully protects against chlamydia infection.

• Chlamydia is the most commonly reported sexually transmitted infection in the US. More than 1.7 million cases were diagnosed in 2017, with 45% recorded among young women ages 15-24 years.

• The National Institute of Allergy and Infectious Diseases has announced $41.6 million over five years to develop vaccines to prevent syphilis, gonorrhea, and chlamydia. The funding will establish four research centers to develop vaccines.


Reproductive healthcare providers are all too familiar with chlamydia, the most commonly reported sexually transmitted infection (STI) in the United States. More than 1.7 million cases were diagnosed in 2017, with 45% recorded among young women ages 15-24 years.1

Results of an early clinical trial of a potential chlamydia vaccine indicate it is safe for use.2 Although the vaccine, the first to reach Phase 1 clinical trial status, demonstrates promising early signs, further studies are needed to determine whether the immune response fully protects against chlamydia infection.

The chlamydia vaccine is based on a recombinant protein subunit (CTH522) in a prime-boost immunization schedule. Scientists looked at two different formulations: one with added liposomes designed to aid cellular immunity, and the other formulated with aluminum hydroxide, which helps to produce antibodies. A total of 35 healthy women ages 19-45 years were randomly assigned to three groups: two with the new vaccine, and one to placebo. Vaccinations were given to participants in three intramuscular injections in the arm, administered on day 0, 28, and 112, with two intranasal boosts given on day 126 and 140. A total of 32 participants received all five vaccinations.

Both formulations of the vaccine provoked an immune response in all participants, whereas no participants in the placebo group achieved an immune response. Researchers noted that while both vaccine formulations provoke immune response, the formulation with the added liposomes consistently performed better, producing 5.6 times more antibodies.

Studies of antibodies in mice have found that antibodies in the vagina are the first line of defense against chlamydia infection, which suggests that they are key to how effective the new vaccine may be, says Helene Juel, PhD, a scientist at Statens Serum Institut in Copenhagen, Denmark, and lead author of the report. Significantly increased concentrations of these antibodies were found in women vaccinated with both formulations of the vaccine, notes Juel. Researchers are planning a Phase 2a study of the vaccine, with the added liposomes as the next stage of research.

The National Institute of Allergy and Infectious Diseases in May 2019 announced awards of $41.6 million over five years to develop vaccines to prevent STIs. The funding will establish four research centers to study the bacteria that cause syphilis, gonorrhea, and chlamydia.

The center focused on chlamydia vaccine research is based at the University of North Carolina (UNC) at Chapel Hill. Leading the center’s efforts is Toni Darville, MD, chief of the UNC Division of Pediatric Infectious Diseases, vice chair of pediatric research, and a distinguished professor of pediatrics, microbiology and immunology at the UNC School of Medicine. Darville and scientists at the University of Pittsburgh previously studied the T-cell response against chlamydia.3 Since chlamydia multiplies inside host cells in a protective vacuole, researchers are looking for a robust type 1 T-cell response for protection.

In the first of three projects funded through the UNC center, Darville and researchers at the University of Pittsburgh will further study candidate vaccine antigens identified in their previous project. Scientists will enroll 150 women at high risk of chlamydia infection into a longitudinal study. All women will be tested for chlamydia, be treated with an antibiotic to clear infection, and followed at four time points over the next year to check for reinfection. Samples will be sent to UNC for further T-cell antigen testing, while collaborators at the German Cancer Research Center in Heidelberg will examine antibody responses.

While animals and humans can develop partial or complete immunity to chlamydia after prolonged or repeated infection, many people can be infected repeatedly — especially if his or her partner is not getting treated, noted Darville. Scientists are trying to determine specific T-cell and antibody responses to inform antigens and adjuvants for vaccine development, she explained.

“A preventive vaccine would greatly benefit women who suffer the brunt of disease due to this pathogen,” said Darville in a press statement. “Men rarely suffer negative effects of infection other than transmitting it to their partners.” (The press statement can be found at: https://unc.live/2l8yzJ2.)

REFERENCES

  1. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017. Atlanta: U.S. Department of Health and Human Services; 2018.
  2. 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. Lancet Infect Dis 2019; doi:10.1016/S1473-3099(19)30279-8.
  3. Russell AN, Zheng X, O’Connell CM, et al. Analysis of factors driving incident and ascending infection and the role of serum antibody in Chlamydia trachomatis genital tract infection. J Infect Dis 2016;213:523-531.