Chuwen Liu1,2, Katrin Hufnagel3, Catherine M O'Connell2, Nilu Goonetilleke4, Neha Mokashi2, Tim Waterboer3, Tammy S Tollison5, Xinxia Peng5,6, Harold C Wiesenfeld7, Sharon L Hillier7, Xiaojing Zheng2, Toni Darville2. 1. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 2. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 3. Division of Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany. 4. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 5. Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina, USA. 6. Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA. 7. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA.
Abstract
BACKGROUND: Previous research revealed antibodies targeting Chlamydia trachomatis elementary bodies was not associated with reduced endometrial or incident infection in C. trachomatis-exposed women. However, data on the role of C. trachomatis protein-specific antibodies in protection are limited. METHODS: A whole-proteome C. trachomatis array screening serum pools from C. trachomatis-exposed women identified 121 immunoprevalent proteins. Individual serum samples were probed using a focused array. Immunoglobulin (Ig) G antibody frequencies and endometrial or incident infection relationships were examined using Wilcoxon rank sum test. The impact of the breadth and magnitude of protein-specific IgGs on ascension and incident infection were examined using multivariable stepwise logistic regression. Complementary RNA sequencing quantified C. trachomatis gene transcripts in cervical swab samples from infected women. RESULTS: IgG to pGP3 and CT_005 were associated with reduced endometrial infection; anti-CT_443, anti-CT_486, and anti-CT_123 were associated with increased incident infection. Increased breadth of protein recognition did not however predict protection from endometrial or incident infection. Messenger RNAs for immunoprevalent C. trachomatis proteins were highly abundant in the cervix. CONCLUSIONS: Protein-specific C. trachomatis antibodies are not sufficient to protect against ascending or incident infection. However, cervical C. trachomatis gene transcript abundance positively correlates with C. trachomatis protein immunogenicity. These abundant and broadly recognized antigens are viable vaccine candidates.
BACKGROUND: Previous research revealed antibodies targeting Chlamydia trachomatis elementary bodies was not associated with reduced endometrial or incident infection in C. trachomatis-exposed women. However, data on the role of C. trachomatis protein-specific antibodies in protection are limited. METHODS: A whole-proteome C. trachomatis array screening serum pools from C. trachomatis-exposed women identified 121 immunoprevalent proteins. Individual serum samples were probed using a focused array. Immunoglobulin (Ig) G antibody frequencies and endometrial or incident infection relationships were examined using Wilcoxon rank sum test. The impact of the breadth and magnitude of protein-specific IgGs on ascension and incident infection were examined using multivariable stepwise logistic regression. Complementary RNA sequencing quantified C. trachomatis gene transcripts in cervical swab samples from infected women. RESULTS: IgG to pGP3 and CT_005 were associated with reduced endometrial infection; anti-CT_443, anti-CT_486, and anti-CT_123 were associated with increased incident infection. Increased breadth of protein recognition did not however predict protection from endometrial or incident infection. Messenger RNAs for immunoprevalent C. trachomatis proteins were highly abundant in the cervix. CONCLUSIONS: Protein-specific C. trachomatis antibodies are not sufficient to protect against ascending or incident infection. However, cervical C. trachomatis gene transcript abundance positively correlates with C. trachomatis protein immunogenicity. These abundant and broadly recognized antigens are viable vaccine candidates.
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