A candidate subunit vaccine induces protective immunity against Mycobacterium avium subspecies paratuberculosis in mice

Abstract

Mycobacterium avium subspecies paratuberculosis (MAP) causes paratuberculosis (PTB), which is a granulomatous enteritis in ruminants that threatens the dairy industry’s healthy development and public health safety worldwide. Because the commercial inactivated vaccines are not completely protective and interfere with bovine tuberculosis diagnostics, we tested four fusion proteins, namely 66NC, 66CN, 90NC, and 90CN, which were constructed with MAP3527, Ag85B, and Hsp70 of MAP in different tandem combinations. Notably, 66NC, which encodes a 66 kDa fusion protein that combines in linear order MAP3527N40–232, Ag85B41–330, and MAP3527C231–361, induced a powerful and specific IFN-γ response. Immunization of C57BL/6 mice with the 66NC fusion protein formulated in Montanide ISA 61 VG adjuvant generated robust Th1, Th2, and Th17 type immune responses and strong antibody responses. The 66NC vaccine protected C57BL/6 mice against virulent MAP K-10 infection. This resulted in a reduction of bacterial load and improvement of pathological damage in the liver and intestine, in addition to a reduction of body weight loss; significantly better protection than the reported 74 F vaccine was also induced. Furthermore, vaccine efficacy correlated with the levels of IFN-γ-, TNF-α-, and IL-17A-secreting antigen-specific CD4+ and CD8+ T lymphocytes as well as with serum IFN-γ and TNF-α levels after vaccination. These results demonstrate that recombinant protein 66NC is an efficient candidate for further development into a protective vaccine in terms of inducing specific protection against MAP.

Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses

“…The immune protection against R. equi infection does not rely exclusively on the CD4 + Th1 lymphocyte response [ 46 ]. As with M. tb , IFN-γ-positive CD8 + T lymphocytes also contribute to immune clearance during pulmonary challenge by virulent R. equi [ 47 , 48 ]. In this study, FCM was used to detect antigen-specific IFN-γ and TNF-α in splenic T lymphocytes, and the proportions of IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes were significantly increased after immunization.…”

A Recombinant Chimera Vaccine Composed of LTB and Mycoplasma hyopneumoniae Antigens P97R1, mhp390 and P46 Elicits Cellular Immunologic Response in Mice

“…The development of recombinant subunit vaccines, comprising highly effective antigen compositions generated through diverse expression systems, has garnered increasing attention in recent years [ 24 , 25 ]. Subunit vaccines are considered safer as they do not contain live pathogens and lack the ability to replicate in the organism [ 16 ].…”

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

“…[6]. Shao et al [7] reported differences in the CFU load in the liver from 2 to 8 w.p.i with the intraperitoneal route, with no bacterial recovery after that. They also detected differences in weight gain among the groups from 2 to 12 w.p.i.…”