Alternative Vaccination Routes against Paratuberculosis Modulate Local Immune Response and Interference with Tuberculosis Diagnosis in Laboratory Animal Models

Abstract

Paratuberculosis (PTB) is an enteric granulomatous disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) that mainly affects ruminants. Current vaccines have shown to be cost–effective control reagents, although they are restricted due to cross-interference with bovine tuberculosis (bTB). Therefore, novel vaccination strategies are needed and this study is focused on evaluating alternative vaccination routes and their effect on the local immune response. The MAP oral challenge rabbit model was used to evaluate and compare an experimental inactivated MAP vaccine through oral (VOR) and intradermal (VID) routes. The VID group presented the highest proportion of animals with no visible lesions and the lowest proportion of animals with MAP positive tissues. Immunohistochemistry analysis revealed that the VID group presented a dominantly M1 polarized response indicating an ability to control MAP infection. In general, all vaccinated groups showed lower calprotectin levels compared to the non-vaccinated challenged group suggesting less active granulomatous lesions. The VID group showed some degree of skin test reactivity, whereas the same vaccine through oral administration was completely negative. These data show that PTB vaccination has an effect on macrophage polarization and that the route influences infection outcome and can also have an impact on bTB diagnosis. Future evaluation of new immunological products against mycobacterial diseases should consider assaying different vaccination routes.

Oral vaccination stimulates neutrophil functionality and exerts protection in a Mycobacterium avium subsp. paratuberculosis infection model

“…The subclinical nature of the infection model is probably contributing to this fact. CV showed the highest lymphoproliferative expression in comparison to the oral vaccines probably due to the administration route and the persistence of the granuloma generated at the injection site, which has shown to correlate in size to anti-PPA3 antibody levels in the previous works 19 .…”

“…Besides, these vaccines present some negative aspects to overcome, such as, some interference with bTB diagnostic tests 15 . This problem may be solved by changing the vaccination route from subcutaneous to oral 19 , though mucosal immunity activation through this route must be tested. In our study we have shown that mucosal activation is possible through oral vaccination (even with inactivated vaccines), and that vaccination against PTB with experimental vaccines (Map inactivated and C. pseudotuberculosis inactivated) and with a Map commercial vaccine is able to enhance neutrophil functionality (showing trained immunity effects) as seen by increased phagocytosis and ET release, important mechanisms for bacterial clearance.…”

“…The MPV vaccine (inactivated Map strain 316F vaccine) was prepared as described previously in Arrazuria et al 19 . The CPV vaccine (inactivated Corynebacterium pseudotuberculosis field strain vaccine) was grown in brain heart infusion (BHI) until mid-exponential phase and was inactivated following the same inactivation protocol as that described for MPV 19 . The MBV vaccine (inactivated Mbv strain 1403 vaccine) was prepared as described in Garrido et al 71 .…”

“…1 . Thirty five rabbits were housed in cages being divided into seven groups of five animals each: non-vaccinated and non-challenged group (NC), non-vaccinated challenged group (CC), subcutaneously vaccinated group with the commercially available vaccine Silirum® (CV) and four orally vaccinated groups: live attenuated vaccine (LAV) 72 , inactivated Map strain 316F vaccine (MPV) 19 , inactivated Mbv strain 1403 vaccine (MBV) and inactivated C. pseudotuberculosis field strain vaccine (CPV). Before challenge, at initial time points, NC and CC, were considered as one group and named NV (non-vaccinated).…”

“…Interference can be avoided or reduced by the introduction of variations in the diagnostic methods 15 , 16 , but this requires modifications in legislation that are difficult to achieve. Another approach to avoid interference with bTB diagnosis, is to apply vaccines through alternative routes as shown for an inactivated M. bovis (Mbv) vaccine in cattle 17 and goats 18 or a Map inactivated vaccine in guinea pigs 19 . In PTB, the oral route is a good alternative since it is the route of natural infection.…”