The Live Attenuated Actinobacillus pleuropneumoniae Triple-Deletion Mutant Δ apxIC Δ apxIIC Δ apxIV - ORF1 Strain, SLW05, Immunizes Pigs against Lethal Challenge with Haemophilus parasuis

Haemophilus parasuis andActinobacillus pleuropneumoniae both belong to the familyPasteurellaceae and are major respiratory pathogens that cause large economic losses in the pig industry worldwide. We previously constructed an attenuatedA. pleuropneumoniae serovar 1 live vaccine prototype, SLW05 (ΔapxIC ΔapxIIC ΔapxIV -ORF1 ), which is able to produce nontoxic but immunogenic ApxIA, ApxIIA, and ApxIVA. This triple-deletion mutant strain was shown to elicit protective immunity against virulentA. pleuropneumoniae . In the present study, we investigated whether immunization with SLW05 could also protect against lethal challenge with virulentH. parasuis SH0165 (serovar 5) or MD0322 (serovar 4). The SLW05 strain was found to elicit a strong humoral antibody response in pigs and to confer significant protection against challenge with a lethal dose ofH. parasuis SH0165 or MD0322. IgG subtype analysis revealed that SLW05 induces a bias toward a Th1-type immune response and stimulates interleukin 2 (IL-2) and gamma interferon (IFN-γ) production. Moreover, antisera from SLW05-vaccinated pigs efficiently inhibited bothA. pleuropneumoniae andH. parasuis growth in a whole-blood assay. This is the first report that a live attenuatedA. pleuropneumoniae vaccine with SLW05 can protect against lethalH. parasuis infection, which provides a novel approach for developing an attenuatedH. parasuis vaccine.