The humoral immune response is essential for successful vaccine protection against paratuberculosis in sheep

Abstract

Background The role played by the humoral immune response in animals vaccinated against a mycobacterial disease such as paratuberculosis, is not well understood. Sheep vaccinated against Mycobacterium avium subsp. paratuberculosis (MAP) can still become infected and in some cases succumb to clinical disease. The strength and location of the humoral immune response following vaccination could contribute to the ability of sheep to clear MAP infection. We examined the peripheral antibody response along with the localised humoral response at the site of paratuberculosis infection, the ileum, to better understand how this contributes to MAP infection of sheep following vaccination and exposure. Results Through assessing MAP specific serum IgG1 and IgG levels we show that the timing and strength of the humoral immune response directly relates to prevention of infection following vaccination. Vaccinated sheep that subsequently became infected had significantly reduced levels of MAP specific serum IgG1 early after vaccination. In contrast, vaccinated sheep that did not subsequently become infected had significantly elevated MAP specific serum IgG1 following vaccination. Furthermore, at 12 months post MAP exposure, vaccinated and subsequently uninfected sheep had downregulated expression of genes related to the humoral response in contrast to vaccinated infected sheep where expression levels were upregulated. Conclusions The timing and strength of the humoral immune response following vaccination against paratuberculosis in sheep directly relates to subsequent infection status. An initial strong IgG1 response following vaccination was crucial to prevent infection. Additionally, vaccinated uninfected sheep were able to modulate that response following apparent MAP clearance, unlike vaccinated infected animals where there was apparent dysregulation of the humoral response, which is associated with progression to clinical disease.

Early response of monocyte-derived macrophages from vaccinated and non-vaccinated goats against in vitro infection with Mycobacterium avium subsp. paratuberculosis

“…Natural infection with Map showed differences in the cellular and humoral response between exposed and non-exposed animals [ 47 ]. These differences between MDMs from naturally exposed and vaccinated animals could be explained by the fact that vaccination is able to generate a stronger and more effective immune response than the natural sensitization with Map on account of the continuous contact with the pathogen and the potentiating action of the adjuvant [ 7 , 48 ].…”

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

“…In PTB, the possible protective effect of antibodies has been questioned and the shift to humoral response has been related to clinical stages of the disease and severe lesions 49 . However, recent studies have demonstrated that the humoral response is necessary for vaccine protection 50 . Our findings suggest that during the first months after vaccination with CV PMN functionality is increased, we hypothesize that activation may occur through upregulation of surface PRPs but once antibody levels increase, immune phagocytosis would be predominant and, in this case, antibodies would be helpful if phagocytes encounter extracellular Map.…”

The Effect of Lipopolysaccharide Subunit Vaccine of Brucella abortus on Montanide ISA 70 Adjuvant on Sheep

“…Other studies stated that no antibody responses during the fourth week after the inoculation, and there was only a sharp increase at the sixth week after the inoculation (Praja et al, 2017). The intensity of the humoral immune response could be demonstrated by the serum antibody level (Pooley et al, 2019).…”