Chlamydia vaccine: What is on the horizon?
Chlamydia vaccine: What is on the horizon?
Review the number of patients who were screened and treated for chlamydia at your facility in the last two weeks. What if their infection could have been prevented by vaccine?
Chlamydia is the most frequently reported bacterial sexually transmitted disease (STD) in the United States, according to the Centers for Disease Control and Prevention.1 In 2004, 929,462 chlamydial infections were reported to the agency.1 About 75% of infected women and half of infected men have no symptoms; if symptoms do occur, they usually appear within one to three weeks following exposure.1
Women who do have symptoms may note an abnormal vaginal discharge or a burning sensation when urinating. Men with symptoms might detect a penile discharge or a burning sensation when urinating or may have burning and itching around the opening of the penis.1 If the infection goes undetected in women, infection may travel from the cervix into the upper genital tract, which can lead to infertility. Men may develop epididymitis if the infection is undetected.
Researchers at the University of Texas at San Antonio (UTSA) South Texas Center for Emerging Infectious Diseases and the University of Texas Health Science Center at San Antonio (UTHSCSA) are working together to discover a vaccine to prevent chlamydia. Ashlesh Murthy, MD, PhD, a postdoctoral fellow in UTSA's biology department, says the research team has found success in administering a chlamydia prevention vaccine in mice.2 "We have clearly demonstrated the efficacy of our vaccination regimen in accelerated resolution of genital chlamydial infections and reduction of subsequent pathology in the oviducts using mouse models of genital chlamydial infection," Murthy states. "We also have identified the mechanisms of protection."3-4
The research team is initiating studies to study the efficacy of the vaccine against infection in guinea pig models, says Murthy. Murthy and Bernard Arulanandam, PhD, UTSA associate professor of microbiology & immunology, are working with Guangming Zhong, MD, PhD, UTHSCSA professor of microbiology, whose research team has identified antigens or proteins in chlamydia as vaccine candidates. Zhong's team is providing those candidates to the UTSA researchers to analyze for their efficacy.
Scientists at Queensland University of Technology (QUT) in Brisbane, Australia are looking at certain proteins in protection against chlamydial infection.5 Peter Timms, PhD, professor in the university's School of Life Sciences, says, "My research group at QUT has been involved in chlamydia research, including disease in koalas, for over 15 years. We have been working on various aspects of chlamydia vaccine development for much of this period."
The Australian group has received a $300,000 grant to continue its research toward developing a vaccine specifically targeting adolescent women.
Advances on the way
Study of Chlamydia trachomatis has proved challenging because the organism, unlike most bacteria, only grows inside the host cell. Scientists have grappled to understand the organism's physiology, structure, developmental biology, and genetics. The availability of the complete C. trachomatis genome sequence, published in 1998, has boosted research advances.6 With the genome sequence in hand, scientists are able to identify and test candidate proteins based on their similarity to proteins important in protective immunity against other bacterial pathogens.
Scientists were able to use the genetic blueprint of Chlamydia trachomatis to identify a gene that encodes a cell-destroying toxin.7 Researchers believe the presence of the toxin explains why only some chlamydial strains cause chronic illness.
Scientists at Emergent BioSolutions in Rockville, MD, are developing a recombinant protein subunit chlamydia vaccine for all clinically relevant strains of Chlamydia trachomatis. Researchers are developing a vaccine candidate to be administered by injection with a novel adjuvant in a three-dose regimen.
BioVeris Corp. of Gaithersburg, MD, has entered into an exclusive, worldwide license agreement with University of Massachusetts Amherst for patent rights to a proprietary chlamydia vaccine candidate developed by researchers in the school's veterinary and animal sciences and microbiology departments. The vaccine under investigation uses a pan-genus antigen that could be effective in preventing infections caused by most or all species of chlamydia. Researchers at the University of Alabama at Birmingham are defining and characterizing chlamydia protective antibody-mediated response in their search for a possible chlamydia vaccine.8
More effort is needed to bring a potential vaccine candidate to market, says Murthy. "The incidence rates of genital chlamydial infections have doubled over the last decade, strongly indicating the need for timely development of an efficacious chlamydial vaccine," Murthy states.
References
- Centers for Disease Control and Prevention. Chlamydia. Fact sheet. Accessed at: www.cdc.gov/std/chlamydia/STDFact-Chlamydia.htm.
- Murthy AK, Chambers JP, Meier PA, et al. Intranasal vaccination with a secreted chlamydial protein enhances resolution of genital Chlamydia muridarum infection, protects against oviduct pathology, and is highly dependent upon endogenous gamma interferon production. Infect Immun 2007; 75:666-676.
- Murphey C, Murthy AK, Meier PA, et al. The protective efficacy of chlamydial protease-like activity factor vaccination is dependent upon CD4+ T cells. Cell Immunol 2006; 242:110-117.
- Murthy AK, Cong Y, Murphey C, et al. Chlamydial protease-like activity factor induces protective immunity against genital chlamydial infection in transgenic mice that express the human HLA-DR4 allele. Infect Immun 2006; 74:6,722-6,729.
- McNeilly C, Beagley K, Moore R, et al. Expression library immunization confers partial protection against Chlamydia muridarum genital infection. Vaccine 2007; dx.doi.org/10.1016/j.vaccine.2006.12.019.
- Stephens RS, Kalman S, Lammel C, et al. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 1998; 282:754-759.
- Belland RJ, Scidmore MA, Crane DD, et al. Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxin genes. Proc Natl Acad Sci USA 2001; 98:13,984-13,989.
- Morrison SG, Morrison RP. A predominant role for antibody in acquired immunity to chlamydial genital tract reinfection. J Immunol 2005; 175:7,536-7,542.
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