Protection Against Chlamydia trachomatis Infection and Upper Genital Tract Pathological Changes by Vaccine-Promoted Neutralizing Antibodies Directed to the VD4 of the Major Outer Membrane Protein

• Published in: The Journal of infectious diseases Vol. 212; no. 6; pp. 978 - 989
• Main Authors: Olsen, Anja W., Follmann, Frank, Erneholm, Karin, Rosenkrands, Ida, Andersen, Peter
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.09.2015
• Subjects: Animals; Antibodies, Bacterial - immunology; Antibodies, Bacterial - physiology; Antibodies, Neutralizing - physiology; BACTERIA; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - immunology; Bacterial Vaccines - immunology; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chlamydia Infections - pathology; Chlamydia Infections - prevention & control; Chlamydia trachomatis - immunology; Chlamydia trachomatis - metabolism; Female; Mice; broadly neutralizing Ab; vaccine; Chlamydia trachomatis; VD4
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiv137

The VD4 region from the Chlamydia trachomatis major outer membrane protein contains important neutralizing B-cell epitopes of relevance for antibody-mediated protection against genital tract infection. We developed a multivalent vaccine construct based on VD4s and their surrounding constant segments from serovars D, E, and F. Adjuvanted with cationic liposomes, this construct promoted strong immune responses to serovar-specific epitopes, the conserved LNPTIAG epitope and neutralized serovars D, E, and F. Vaccinated mice were protected against challenge, with protection defined as reduced bacterial numbers in vagina and prevention of pathological changes in the upper genital tract. Adoptive transfer of serum and T-cell depletion experiments demonstrated a dominant role for antibodies and CD4⁺ T cells in the protective immune response. Integrating a multivalent VD4 construct into the sequence of the major outer membrane protein resulted in a protective and broadly neutralizing vaccine. Our findings emphasize the important role of antibodies in protection against Chlamydia trachomatis.