PROTECTION OF MICE AGAINST CHALLENGE WITH HOMOLOGOUS AND HETEROLOGOUSSEROVARS OF ACTINOBACILLUS-PLEUROPNEUMONIAE AFTER LIVE VACCINATION

Protective immune responses and the virulence of Actinobacillus pleuro pneumoniae (APP) have been attributed, in part, to toxins (Apx) produc ed by the bacterium. A mutant of the serovar 7 strain HS93 (HS93Tox(-) ), lacking the genes encoding the structural toxin ApxA and the post-t ranslational activating protein ApxC, but retaining the genes required for secretion ApxB and ApxD, was isolated and shown to be attenuated in a mouse model. A plasmid vector system was developed and used to ex press the ApxA gene from within the HS93Tox(-) strain. The resulting s train, HS93Tox(-)/pIG-T1K, expresses the Apr structural protein in a n on-activated form. HS93Tox(-)/pIG-T1K was shown to be attenuated in a mouse model and to be capable of inducing Apr-specific antibodies, whi ch were boosted on reinoculation. Live vaccination of mice with HS93To x(-)/pIG-T1K offered protection against homologous wild-type serovar 7 challenge, and also heterologous challenge with a serovar 1 strain. T his is in contrast to vaccination with the HS93Tox(-) strain, which fa iled to protect mice against a heterologous challenge.