Use of an Actinobacillus pleuropneumoniae multiple mutant as a vaccine that allows differentiation of vaccinated and infected animals.
Vaccination against Actinobacillus pleuropneumoniae is hampered by the lack of vaccines inducing reliable cross-serotype protection. In contrast, pigs surviving natural infection are at least partially protected from clinical symptoms upon reinfection with any serotype. Thus, we set out to construct an attenuated A. pleuropneumoniae live vaccine allowing the differentiation of vaccinated from infected animals (the DIVA concept) by successively deleting virulence-associated genes. Based on an A. pleuropneumoniae serotype 2 prototype live negative marker vaccine (W. Tonpitak, N. Baltes, I. Hennig-Pauka, and G.-F. Gerlach, Infect. Immun. 70:7120-7125, 2002), genes encoding three enzymes involved in anaerobic respiration and the ferric uptake regulator Fur were deleted, resulting in a highly attenuated sixfold mutant; this mutant was still able to colonize the lower respiratory tract and induced a detectable immune response. Upon a single aerosol application, this mutant provided significant protection from clinical symptoms upon heterologous infection with an antigenically distinct A. pleuropneumoniae serotype 9 challenge strain and allowed the serological discrimination between infected and vaccinated groups.
Maas
Alexander
A
Institut fuer Mikrobiologie, Zentrum fuer Infektionsmedizin, Stiftung Tierärztliche Hochschule Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany.
Jacobsen
Ilse D
ID
Meens
Jochen
J
Gerlach
Gerald-F
GF
D000189:Actinobacillus Infections / Q000276:immunology / Q000517:prevention & control* / Q000662:veterinary; D016977:Actinobacillus pleuropneumoniae / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D009154:Mutation; D012097:Repressor Proteins / Q000502:physiology; D013552:Swine / Q000276:immunology* / Q000382:microbiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D012097:Repressor Proteins; D014613:Vaccines, Attenuated; C068477:ferric uptake regulating proteins, bacterial