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

Abstract

Mycobacterium avium subsp. paratuberculosis (Map) causes paratuberculosis (PTB), a granulomatous enteritis in ruminants that exerts high economic impact on the dairy industry worldwide. Current vaccines have shown to be cost-effective against Map and in some cases confer beneficial non-specific effects against other pathogens suggesting the existence of trained immunity. Although Map infection is mainly transmitted by the fecal-oral route, oral vaccination has not been deeply studied. Therefore, the aim of this study was to compare the oral route with a set of mycobacterial and non-mycobacterial vaccines with a subcutaneously administered commercially available vaccine. Training effects on polymorphonuclear neutrophils (PMNs) and homologous and heterologous in vivo protection against Map were investigated in the rabbit infection model. Oral vaccination with inactivated or live vaccines was able to activate mucosal immunity as seen by elevation of serum IgA and the expression of IL4 in peripheral blood mononuclear cells (PBMCs). In addition, peripheral PMN phagocytosis against Map was enhanced by vaccination and extracellular trap release against Map and non-related pathogens was modified by both, vaccination and Map-challenge, indicating trained immunity. Finally, PBMCs from vaccinated animals stimulated in vitro with Map antigens showed a rapid innate activation cytokine profile. In conclusion, our data show that oral vaccination against PTB can stimulate neutrophil activity and both innate and adaptive immune responses that correlate with protection.

Cathepsin S Is More Abundant in Serum of Mycobacterium avium subsp. paratuberculosis-Infected Dairy Cows

“…In a strong innate response to MAP, caprine neutrophils use all their effector functions-phagocytosis, chemotaxis, degranulation and NET release [65]. Oral vaccination against MAP in a rabbit infection model stimulated the phagocytosis rate of neutrophils and additionally increased NET release against MAP and non-related pathogens [66].…”

Non-specific effects of inactivated Mycobacterium bovis oral and parenteral treatment in a rabbit scabies model

“…It also warns on the timing of the optimal response regarding experimental designs because it seems possible that the desirable long-term effects cannot be seen with shorter experiment follow-ups. Additionally, it seems that the oral route might be a good delivery way [ 40 , 41 ], thus supporting the beneficial effects of use of immune enhancers in the diet [ 1 ]. This is also consistent with a mechanism developed and operating in natural conditions by chance when the right conditions concur.…”

Modeling Paratuberculosis in Laboratory Animals, Cells or Tissues: Focus on Their Applications for Pathogenesis, Diagnosis, Vaccines and Therapies Studies

“…Further studies have used this challenge route to evaluate the impact of diet [16] or a probiotic [22] on MAP infection, MAP infection on the microbiome [23], the vaccination sequence on the progression of MAP infection and the immunological response [24], and the passively transferred antibodies on MAP colonization [25]. This oral challenge model has also been complemented with ex vivo assays that have permitted the functional analysis of immune cells and the study of trained immunity exerted by vaccination [26]. When using this model, it should be considered that the reliable reproduction of the typical clinical, pathological, and microbiological signs seems to depend greatly on the strain's origin and passage, obtaining higher degrees of infection when low-passage cattle field strains are used.…”

“…Caprine neutrophils have also demonstrated a strong innate response against MAP, using their entire repertoire of effector functions, ET release, degranulation, chemotaxis, and phagocytosis [95]. Vaccination against PTB in rabbits increased the phagocytic activity of these immune cells, along with their ability to release ET against mycobacterial and non-mycobacterial agents [26]. In this study, the degree of protection of the different vaccine prototypes was correlated to the ex vivo antimicrobial activity of the neutrophils, indicating that this cell type may play a role in protection.…”