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An Important Step Toward A Vaccine For Chlamydia

  February, 13 2006 17:05
your information resource in human molecular genetics
Chlamydia trachomatis polymorphic membrane protein D is a species-common pan-neutralizing antigen. Crane, D.D., Carlson, J.H., Fischer, E.R., Bavoil, P., Hsia, R., Tan, C., Kuo, C., and Caldwell, H.D. Proc. Nat. Acad. Sci., 103(6), 1894-1899 (February 7, 2006).

Development of a vaccine against Chlamydia trachomatis infections has been hindered by the presence of multiple serotypes of the bacterium. Initial work focused on the immunodominant major outer membrane protein (MOMP). This approach, however, proved to be of limited usefulness, due to antigenic variability between the serotypes. Indeed, immunity to MOMP is homotypic and short-lived.

An investigation of a 155 kDa species-common C. trachomatis antigen identified the protein as polymorphic membrane protein D (pmpD). Antibodies against this membrane-surface protein were found to be species-specific, in that they do not bind to C. muridarum, pneumoniae, or caviae. But they do bind with and neutralize the three major serotypes of C. trachomatis, ocular (A, Ba, and C), genital noninvasive (D, E, F, G, and K), and genital invasive (L2).

A study of the interaction of antibodies to MOMP and another cell-surface antigen, lipopolysaccharide, and antibodies against pmpD suggests that the immunodominant antigens serve as decoys to protect C. trachomatis. That is, pre-exposure to antibodies against MOMP or the lipopolysaccharide block the neutralizing activity of antiserum against pmpD, although anti-MOMP proved less effective due to its own neutralizing activity. In contrast, incubation with antibodies against MOMP and lipopolysaccharide after exposure to anti-pmpD had no effect on neutralizing activity.

This work indicates that the polymorphic membrane protein D is a pan-neutralizing, species-specific antigen that may form the basis of a prophylactic vaccine against C. trachoma infections. However, due to the protective capacity of antibodies to the immunodominant antigens MOMP and lipopolysaccharide, a vaccine targeting pmpD probably would have limited therapeutic value in combating an established chlamydial infection.

Message posted by: Keith Markey

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