A POLIOVIRUS HYBRID EXPRESSING A NEUTRALIZATION EPITOPE FROM THE MAJOR OUTER-MEMBRANE PROTEIN OF CHLAMYDIA-TRACHOMATIS IS HIGHLY IMMUNOGENIC

Trachoma and sexually transmitted diseases caused by Chlamydia trachom atis are major health problems worldwide. Epitopes on the major outer membrane protein (MOMP) of C. trachomatis have been identified as impo rtant targets for the development of vaccines. In order to examine the immunogenicity of a recombinant vector expressing a chlamydial epitop e, a poliovirus hybrid was constructed in which part of neutralization antigenic site I of poliovirus type 1 Mahoney (PV1-M) was replaced by a sequence from variable domain I of the MOMP of C. trachomatis serov ar A. The chlamydial sequence included the neutralization epitope VAGL EK. This hybrid was viable, grew very well compared with PV1-M, and ex pressed both poliovirus and chlamydial antigenic determinants. When in oculated into rabbits, this hybrid was highly immunogenic, inducing a strong response against both PV1-M and C. trachomatis serovar A. Antic hlamydia titers were 10- to 100-fold higher than the titers induced by equimolar amounts of either purified MOMP or a synthetic peptide expr essing the VAGLEK epitope. Furthermore, rabbit antisera raised against this hybrid neutralized chlamydial infectivity both in vitro, for ham ster kidney cells, and passively in vivo, for conjunctival epithelia o f cynomolgus monkeys. Because poliovirus infection induces a strong mu cosal immune response in primates and humans, these results indicate t hat poliovirus-chlamydia hybrids could become powerful tools for the s tudy of mucosal immunity to chlamydial infection and for the developme nt of recombinant chlamydial vaccines.