Chlamydia Vaccine on the Horizon?

BACKGROUND

Chlamydia trachomatisis a Gram-negative, obligate intracellular pathogenic bacterium that is responsible for one of the most widespread sexually-transmitted bacterial infections. Worldwide, it is estimated that 100 million people are infected with genital Chlamydia trachomatis (1).Even though active infections can be controlled with antibiotics, they do not provide long-term protection against re-infection. Many who are infected with Chlamydiaremain asymptomatic and can still infect others through sexual contact. Untreated Chlamydiainfections can lead to infertility and may even increase susceptibility to other sexually-transmitted infections (2).

PROMISING VACCINE RESEARCH

Earlier studies confirmed that an effective Chlamydiavaccine must elicit humoral and cell-mediated immunity in order to be effective (3).  Neutralizing antibodies reduce the bacterial load, while a bactericidal cell-mediated response targets intracellularChlamydia.  The Chlamydialmajor outer membrane protein (MOMP), which is highly immunogenic, has been studied in detail as a potential vaccine candidate, however it is an integral membrane protein, and immunogenicity depends on a correctly folded structure which is not readily replicated in a recombinant protein.

A recent Phase 1 trial performed at Hammersmith Hospital in London, UK with a recombinant MOMP fusion antigen showed very promising results in women not previously infected with Chlamydia(4).  The antigen was a truncated and cysteine-free version of MOMP fused to four variable domains from Chlamydiaserovars D-G, which had previously been shown to be protective in a mouse model (1), and was tested in two different formulations: adjuvanted with either liposomes or with aluminum hydroxide. Three intramuscular injections were administered over several months followed by two intranasal boosts. Both formulations were well-tolerated and stimulated elevated serum antibody titers as well as cell-mediated immune responses in all of the recipients.

This was the first trial of its kind, and the results are encouraging.  Subsequent trials will determine if this vaccine candidate will be protective against Chlamydiainfection and thereby be an effective tool for reducing infection rates worldwide.

References

1. Rose F et al. 2018  Unusual Self-Assembly of the recombinant Chlamydia trachomatis Major Outer Membrane Protein-Based Fusion Antigen CTH522 Into Protein Nanoparticles. J Pharm Sci 107: 1690-1700.
2. Malhotra M et al.  2013  Genital Chlamydia trachomatis: An update  Indian J Med Res 138: 303-316.
3. Brunham RC, Rey-Ladino J 2005 Immunology of Chlamydiainfection: implications for a Chlamydia trachomatisvaccine.  Nat Rev Immunol 5: 149-161.
4. Abraham S et al. 2019  CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomized, double-blind, placebo-controlled, phase 1 trial. The Lancet Infectious Diseases DOI:https://doi.org/10.1016/S1473-3099(19)30279-8